Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate t...Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment.展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity...BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses.展开更多
Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^...Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.展开更多
湿疹是一种变态反应性炎症性皮肤病,近期研究表明以CD^(+)_(4)T细胞亚群如Th1/Th2、Th17/调节性T细胞(regulatory T cells,Treg)细胞分化失衡导致湿疹发病中出现过度炎症应答,而中药以改善CD^(+)_(4)T细胞亚群分化平衡干预湿疹免疫微环...湿疹是一种变态反应性炎症性皮肤病,近期研究表明以CD^(+)_(4)T细胞亚群如Th1/Th2、Th17/调节性T细胞(regulatory T cells,Treg)细胞分化失衡导致湿疹发病中出现过度炎症应答,而中药以改善CD^(+)_(4)T细胞亚群分化平衡干预湿疹免疫微环境具有较好的调节作用。以湿疹炎症应答前沿研究动态,探讨中药在改善调控CD^(+)_(4)T细胞亚群分化干预湿疹致病的作用优势,为中药在改善湿疹临床症状及机制研究提供一定的理论指导。展开更多
Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Viruses (HIV) resulting in progressive destruction of cell mediated immunity. The abdominal manifestations of AIDS are related to the level...Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Viruses (HIV) resulting in progressive destruction of cell mediated immunity. The abdominal manifestations of AIDS are related to the level of CD+4 cells count as well as viral load. Abdominal ultrasound examination is easy to perform, non-invasive, inexpensive, readily available and reproducible investigation which provides valuable information about abdominal findings in AIDS. The objective of the study was to evaluate abdominal ultrasound findings in adult HIV/AIDS patients in Jos, Plateau State, Nigeria and correlate these findings with the patients’ CD+4 counts. A cross-sectional study of abdominal ultrasound findings of adult patients with HIV/AIDS was conducted over a period of six months. The abdominal ultrasound findings and CD+4 counts were studied. Two hundred (40%) of the patients had normal abdominal ultrasound, while 60% (300) had various abnormalities. The common abnormalities included increased liver parenchymal echogenicity in 25.0%, hepatomegaly in 23.4%, splenomegaly in 6.6%, increased splenic echogenicity in 6.2% and thickened gallbladder wall in 12.6%, elevated renal parenchymal echogenicity in 6.4%, enlarged kidneys in 2.6%, lymphadenopathy in 6.0%, and ascites in 2.4%. Pelvic abscess was the least pathology in 0.2%. Most of the findings did not correlate with the patients’ CD+4?count except for lymphadenopathy and ascites. Although abdominal ultrasound examination is invaluable in the management of these patients, however, it has not shown to be useful in predicting the patients’ immune status.展开更多
Survival of HIV/AIDS patients is crucially dependent on comprehensive and targeted medical interventions such as supply of antiretroviral therapy and monitoring disease progression with CD4 T-cell counts. Statistical ...Survival of HIV/AIDS patients is crucially dependent on comprehensive and targeted medical interventions such as supply of antiretroviral therapy and monitoring disease progression with CD4 T-cell counts. Statistical modelling approaches are helpful towards this goal. This study aims at developing Bayesian joint models with assumed generalized error distribution (GED) for the longitudinal CD4 data and two accelerated failure time distributions, Lognormal and loglogistic, for the survival time of HIV/AIDS patients. Data are obtained from patients under antiretroviral therapy follow-up at Shashemene referral hospital during January 2006-January 2012 and at Bale Robe general hospital during January 2008-March 2015. The Bayesian joint models are defined through latent variables and association parameters and with specified non-informative prior distributions for the model parameters. Simulations are conducted using Gibbs sampler algorithm implemented in the WinBUGS software. The results of the analyses of the two different data sets show that distributions of measurement errors of the longitudinal CD4 variable follow the generalized error distribution with fatter tails than the normal distribution. The Bayesian joint GED loglogistic models fit better to the data sets compared to the lognormal cases. Findings reveal that patients’ health can be improved over time. Compared to the males, female patients gain more CD4 counts. Survival time of a patient is negatively affected by TB infection. Moreover, increase in number of opportunistic infection implies decline of CD4 counts. Patients’ age negatively affects the disease marker with no effects on survival time. Improving weight may improve survival time of patients. Bayesian joint models with GED and AFT distributions are found to be useful in modelling the longitudinal and survival processes. Thus we recommend the generalized error distributions for measurement errors of the longitudinal data under the Bayesian joint modelling. Further studies may investigate the models with various types of shared random effects and more covariates with predictions.展开更多
Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drug...Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.展开更多
<strong><em>Background: </em></strong>The appropriate time to initiate antiretroviral therapy (ART) in HIV/AIDS patients is determined by measurement of CD4+/CD8+ T cell count. The CD4/CD8+ T c...<strong><em>Background: </em></strong>The appropriate time to initiate antiretroviral therapy (ART) in HIV/AIDS patients is determined by measurement of CD4+/CD8+ T cell count. The CD4/CD8+ T cell count is also useful, together with viral load, in monitoring disease progression and effectiveness treatment regimens. Several factors may contribute to sample rejection during the CD4+/CD8+ T cells count, resulting in negative effects on patient management. <strong> <em>Objective: </em></strong>Evaluate the causes for CD4+CD8+ T cell count sample rejection at the Kenyatta National Hospital Comprehensive Care Center Laboratory. <strong><em>Method:</em></strong> A retrospective cross-sectional study was conducted between 2018 and 2020. Data was obtained from the “rejected samples” for Partec<sup>R</sup> FlowCyp flow cytometry file. Designed data collection sheet was used for data capture. A total of 3972 samples were submitted for CD4+/CD8+ T cell count during the study period. Causes for sample rejection were numbered 1 to 12, each representing a reason for sample rejection. Number 1 was sub-categorized into clotted, hemolyzed, short-draw and lipemic. Data was analyzed using excel, and presented using tables, graphs and pie charts. Approval to conduct the study was obtained from KNH/UoN ERC. <strong> <em>Results: </em></strong>In the study period, 81/3972 (2.0%) samples were rejected. Samples submitted more than 48 hours after collection were mostly rejected. Other factors included improper collection technique, delayed testing, patient identification error and incorrect use of vacutainer. A combination of clotted samples, specimen submission more than 48 hours caused the most frequent sample rejection, followed with combination of specimen submission more than 48 hours, delayed testing and delayed specimen processing. Together, clotted samples, incorrect vacutainer and poor specimen label caused the least sample rejection. <strong><em>Conclusion:</em></strong> Sample rejection rate for CD4/CD8+ T cell count was relatively low, and multiple factors contributed to rejection. However, improved quality assurance will enable more benefit to patients who seek this test in the laboratory.展开更多
Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection...Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection. Objective: We compare the frequency and the activity of NKT cells in HIV-1 and HIV-2 infected individuals with CD4+ counts greater than 500/mm3 using flow cytometry after overnight stimulation with phytohemagglutinin (PHA). Results: The frequency of NKT cells was similar between both groups and also to sero-negative control subjects. There were also no significant differences in the proportions of total NKT cells and the CD4+ NKT subset that secreted interferon gamma (IFN-γ) after polyclonal stimulation. However, there was a significantly higher frequency of IFN-γ﹣ CD4+ NKT cells in HIV-1-infected compared with HIV-2 infected subjects (p = 0.043). Conclusion: These data suggest there is no relationship between the functional activity of NKT cell subsets and the total NKT cell population in HIV infection. The expansion of IFN-γ﹣ CD4+ NKT cells in HIV-1 infection may serve as target for viral infection and may eventually result in their depletion during chronic infection.展开更多
Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant wo...Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.展开更多
Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided ...Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Conclusions: There was a correlation between CHF and the dysfunction of CD4+ T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease.展开更多
Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The a...Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^+CD25^+ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4+ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.展开更多
The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible role...The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4^+CD25^+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P〈0.05). Although the CD4^+CD25^+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P〉0.05). As compared with persistent group, exacerbation group had lower CD4^+CD25^+ Treg ratio and Foxp3 mRNA (P〈0.05). It was indicated that the decrease of CD4^+CD25^+ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.展开更多
The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balanc...The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid (ATRA) on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4+ T cells and normal CD4+ T were treated for 48 h with or without ATRA.展开更多
Recently, the human cochlea has been shown to contain numerous resident macrophages under steady-state. The macrophages accumulate in the stria vascularis, among the auditory nerves, and are also spotted in the human ...Recently, the human cochlea has been shown to contain numerous resident macrophages under steady-state. The macrophages accumulate in the stria vascularis, among the auditory nerves, and are also spotted in the human organ of Corti. These macrophages may process antigens reaching the cochlea by invasion of pathogens and insertion of CI electrode. Thus, macrophages execute an innate, and possibly an adaptive immunity. Here, we describe the molecular markers CD4 and CD8 of T cells, macrophage markers MHCⅡ and CD11b, as well as the microglial markers TEME119 and P2Y12, in the human cochlea. Immunohistochemistry and the advantageous super-resolution structured illumination microscopy(SR-SIM) were used in the study. CD4^+ and CD8^+ cells were found in the human cochleae. They were seen in the modiolus in a substantial number adjacent to the vessels, in the peripheral region of the Rosenthal's canal, and occasionally in the spiral ligament. While there are a surprisingly large number of macrophages in the stria vascularis as well as between the auditory neurons,CD4^+ and CD8^+ cells are hardly seen in these areas, and neither are seen in the organ of Corti. In the modiolus,macrophages, CD4^+ and CD8^+ cells appeared often in clusters. Interaction between these different cells was easily observed with SR-SIM, showing closely placed cell bodies, and the processes from macrophages reaching out and touching the lymphocytes. Otherwise the CD4^+ and CD8^+ cells in human cochlear tissue are discretely scattered. The possible roles of these immune cells are speculated.展开更多
This study investigated the effect of advanced glycation end products(AGEs) on differentiation of na ve CD4+T cells and the role of the receptor of AGEs(RAGE) and peroxisome proliferator-activated receptors(PPAR...This study investigated the effect of advanced glycation end products(AGEs) on differentiation of na ve CD4+T cells and the role of the receptor of AGEs(RAGE) and peroxisome proliferator-activated receptors(PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin(BSA) with glucose. Human na ve CD4+T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin(sh) RNA knock-down experiment, na ve CD4+T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-XTM293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4+T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T(Treg) cells was determined by a [3H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from na ve CD4+T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in na ve CD4+T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4+T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα; PPARγ agonist, PGJ2, inhibited the effect of AGEs on na ve CD4+T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4+T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity. +展开更多
Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.M...Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con...展开更多
BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa- titis C (CHC) infection have not ...BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa- titis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation ofIgG+ B cells in CHC patients is not clear. METHODS: The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circu- lating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system. RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81760009 and 81560007).
文摘Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment.
基金Supported by the First-Class Discipline Construction Founded Project of Ningxia Medical University and the School of Clinical Medicine,No.2020008.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses.
基金supported by the Natural Science Foundation of Sichuan Province (Grant No.2022NSFSC1415)the Special Project of Sichuan Province Traditional Chinese Medicine Administration (Grant No. 2020JC0124)+1 种基金the Management Project of General Hospital of Western Theater Command (Grants No. 2021-XZYG-C22 and 2021-XZYG-C21)the Spark Young Innovative Talent Project of General Hospital of Western Theater Command。
文摘Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.
文摘湿疹是一种变态反应性炎症性皮肤病,近期研究表明以CD^(+)_(4)T细胞亚群如Th1/Th2、Th17/调节性T细胞(regulatory T cells,Treg)细胞分化失衡导致湿疹发病中出现过度炎症应答,而中药以改善CD^(+)_(4)T细胞亚群分化平衡干预湿疹免疫微环境具有较好的调节作用。以湿疹炎症应答前沿研究动态,探讨中药在改善调控CD^(+)_(4)T细胞亚群分化干预湿疹致病的作用优势,为中药在改善湿疹临床症状及机制研究提供一定的理论指导。
文摘Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Viruses (HIV) resulting in progressive destruction of cell mediated immunity. The abdominal manifestations of AIDS are related to the level of CD+4 cells count as well as viral load. Abdominal ultrasound examination is easy to perform, non-invasive, inexpensive, readily available and reproducible investigation which provides valuable information about abdominal findings in AIDS. The objective of the study was to evaluate abdominal ultrasound findings in adult HIV/AIDS patients in Jos, Plateau State, Nigeria and correlate these findings with the patients’ CD+4 counts. A cross-sectional study of abdominal ultrasound findings of adult patients with HIV/AIDS was conducted over a period of six months. The abdominal ultrasound findings and CD+4 counts were studied. Two hundred (40%) of the patients had normal abdominal ultrasound, while 60% (300) had various abnormalities. The common abnormalities included increased liver parenchymal echogenicity in 25.0%, hepatomegaly in 23.4%, splenomegaly in 6.6%, increased splenic echogenicity in 6.2% and thickened gallbladder wall in 12.6%, elevated renal parenchymal echogenicity in 6.4%, enlarged kidneys in 2.6%, lymphadenopathy in 6.0%, and ascites in 2.4%. Pelvic abscess was the least pathology in 0.2%. Most of the findings did not correlate with the patients’ CD+4?count except for lymphadenopathy and ascites. Although abdominal ultrasound examination is invaluable in the management of these patients, however, it has not shown to be useful in predicting the patients’ immune status.
文摘Survival of HIV/AIDS patients is crucially dependent on comprehensive and targeted medical interventions such as supply of antiretroviral therapy and monitoring disease progression with CD4 T-cell counts. Statistical modelling approaches are helpful towards this goal. This study aims at developing Bayesian joint models with assumed generalized error distribution (GED) for the longitudinal CD4 data and two accelerated failure time distributions, Lognormal and loglogistic, for the survival time of HIV/AIDS patients. Data are obtained from patients under antiretroviral therapy follow-up at Shashemene referral hospital during January 2006-January 2012 and at Bale Robe general hospital during January 2008-March 2015. The Bayesian joint models are defined through latent variables and association parameters and with specified non-informative prior distributions for the model parameters. Simulations are conducted using Gibbs sampler algorithm implemented in the WinBUGS software. The results of the analyses of the two different data sets show that distributions of measurement errors of the longitudinal CD4 variable follow the generalized error distribution with fatter tails than the normal distribution. The Bayesian joint GED loglogistic models fit better to the data sets compared to the lognormal cases. Findings reveal that patients’ health can be improved over time. Compared to the males, female patients gain more CD4 counts. Survival time of a patient is negatively affected by TB infection. Moreover, increase in number of opportunistic infection implies decline of CD4 counts. Patients’ age negatively affects the disease marker with no effects on survival time. Improving weight may improve survival time of patients. Bayesian joint models with GED and AFT distributions are found to be useful in modelling the longitudinal and survival processes. Thus we recommend the generalized error distributions for measurement errors of the longitudinal data under the Bayesian joint modelling. Further studies may investigate the models with various types of shared random effects and more covariates with predictions.
文摘Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.
文摘<strong><em>Background: </em></strong>The appropriate time to initiate antiretroviral therapy (ART) in HIV/AIDS patients is determined by measurement of CD4+/CD8+ T cell count. The CD4/CD8+ T cell count is also useful, together with viral load, in monitoring disease progression and effectiveness treatment regimens. Several factors may contribute to sample rejection during the CD4+/CD8+ T cells count, resulting in negative effects on patient management. <strong> <em>Objective: </em></strong>Evaluate the causes for CD4+CD8+ T cell count sample rejection at the Kenyatta National Hospital Comprehensive Care Center Laboratory. <strong><em>Method:</em></strong> A retrospective cross-sectional study was conducted between 2018 and 2020. Data was obtained from the “rejected samples” for Partec<sup>R</sup> FlowCyp flow cytometry file. Designed data collection sheet was used for data capture. A total of 3972 samples were submitted for CD4+/CD8+ T cell count during the study period. Causes for sample rejection were numbered 1 to 12, each representing a reason for sample rejection. Number 1 was sub-categorized into clotted, hemolyzed, short-draw and lipemic. Data was analyzed using excel, and presented using tables, graphs and pie charts. Approval to conduct the study was obtained from KNH/UoN ERC. <strong> <em>Results: </em></strong>In the study period, 81/3972 (2.0%) samples were rejected. Samples submitted more than 48 hours after collection were mostly rejected. Other factors included improper collection technique, delayed testing, patient identification error and incorrect use of vacutainer. A combination of clotted samples, specimen submission more than 48 hours caused the most frequent sample rejection, followed with combination of specimen submission more than 48 hours, delayed testing and delayed specimen processing. Together, clotted samples, incorrect vacutainer and poor specimen label caused the least sample rejection. <strong><em>Conclusion:</em></strong> Sample rejection rate for CD4/CD8+ T cell count was relatively low, and multiple factors contributed to rejection. However, improved quality assurance will enable more benefit to patients who seek this test in the laboratory.
文摘Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection. Objective: We compare the frequency and the activity of NKT cells in HIV-1 and HIV-2 infected individuals with CD4+ counts greater than 500/mm3 using flow cytometry after overnight stimulation with phytohemagglutinin (PHA). Results: The frequency of NKT cells was similar between both groups and also to sero-negative control subjects. There were also no significant differences in the proportions of total NKT cells and the CD4+ NKT subset that secreted interferon gamma (IFN-γ) after polyclonal stimulation. However, there was a significantly higher frequency of IFN-γ﹣ CD4+ NKT cells in HIV-1-infected compared with HIV-2 infected subjects (p = 0.043). Conclusion: These data suggest there is no relationship between the functional activity of NKT cell subsets and the total NKT cell population in HIV infection. The expansion of IFN-γ﹣ CD4+ NKT cells in HIV-1 infection may serve as target for viral infection and may eventually result in their depletion during chronic infection.
基金supported by Science and Technology Project of Jiangxi Province(2009BSB10909)
文摘Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.
基金supported by the Brainstorm Project of Guizhou Science and Technology Office (Grant No.SY 20133016)Guiyang Science and Technology Planning Project (Grand No.20151001)
文摘Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Conclusions: There was a correlation between CHF and the dysfunction of CD4+ T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease.
基金supported by the National Natural Science Foundation of China (No.30330540)the Jiangsu Provincial Fund for Clinical Immunology Key Laboratory (No.200319)the Scientific and Technological Fund to Support Project of Suzhou City (ZS0901)
文摘Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^+CD25^+ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4+ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.
基金This project was supported by a program of Science Project of Hubei Province (No.2003AA301C10).
文摘The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4^+CD25^+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P〈0.05). Although the CD4^+CD25^+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P〉0.05). As compared with persistent group, exacerbation group had lower CD4^+CD25^+ Treg ratio and Foxp3 mRNA (P〈0.05). It was indicated that the decrease of CD4^+CD25^+ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.
基金supported by the National Natural Science Foundation of China(No.30671761)
文摘The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid (ATRA) on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4+ T cells and normal CD4+ T were treated for 48 h with or without ATRA.
基金supported by ALF and private funds from Borje Runogard,Swedenpartly supported by MED-EL,Inc.,Innsbruck,Austria
文摘Recently, the human cochlea has been shown to contain numerous resident macrophages under steady-state. The macrophages accumulate in the stria vascularis, among the auditory nerves, and are also spotted in the human organ of Corti. These macrophages may process antigens reaching the cochlea by invasion of pathogens and insertion of CI electrode. Thus, macrophages execute an innate, and possibly an adaptive immunity. Here, we describe the molecular markers CD4 and CD8 of T cells, macrophage markers MHCⅡ and CD11b, as well as the microglial markers TEME119 and P2Y12, in the human cochlea. Immunohistochemistry and the advantageous super-resolution structured illumination microscopy(SR-SIM) were used in the study. CD4^+ and CD8^+ cells were found in the human cochleae. They were seen in the modiolus in a substantial number adjacent to the vessels, in the peripheral region of the Rosenthal's canal, and occasionally in the spiral ligament. While there are a surprisingly large number of macrophages in the stria vascularis as well as between the auditory neurons,CD4^+ and CD8^+ cells are hardly seen in these areas, and neither are seen in the organ of Corti. In the modiolus,macrophages, CD4^+ and CD8^+ cells appeared often in clusters. Interaction between these different cells was easily observed with SR-SIM, showing closely placed cell bodies, and the processes from macrophages reaching out and touching the lymphocytes. Otherwise the CD4^+ and CD8^+ cells in human cochlear tissue are discretely scattered. The possible roles of these immune cells are speculated.
文摘This study investigated the effect of advanced glycation end products(AGEs) on differentiation of na ve CD4+T cells and the role of the receptor of AGEs(RAGE) and peroxisome proliferator-activated receptors(PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin(BSA) with glucose. Human na ve CD4+T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin(sh) RNA knock-down experiment, na ve CD4+T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-XTM293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4+T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T(Treg) cells was determined by a [3H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from na ve CD4+T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in na ve CD4+T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4+T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα; PPARγ agonist, PGJ2, inhibited the effect of AGEs on na ve CD4+T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4+T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity. +
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.200804871044)
文摘Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con...
基金supported by grants from the National Science and Technology Major Project for Infectious Diseases Control during the 11th Five-Year Plan(2008ZX10002-012 and 2008ZX10002-013)the 12th Five-Year Plan(2012ZX10002003)
文摘BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa- titis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation ofIgG+ B cells in CHC patients is not clear. METHODS: The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circu- lating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system. RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.