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
BACKGROUND Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms,but the treatment and anti-infective medication are completely different.Here,we report a case ...BACKGROUND Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms,but the treatment and anti-infective medication are completely different.Here,we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica(N.cyriacigeorgica),which was misdiagnosed as community-acquired pneumonia(CAP)with repeated fever.CASE SUMMARY A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months.After the anti-infection treatment failed in the local hospital,the patient came to our hospital for further treatment.Enhanced computed tomography showed multiple patchy,nodular and strip-shaped high-density shadows in both lungs.A routine haematological examination was performed and showed abnormalities in CD19+B cells and CD4+T cells.Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope,which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N.cyriacigeorgica.The patient’s condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day.CONCLUSION The antibiotic treatment of Nocardia pneumonia is different from that of common CAP.Attention should be given to the pathogenic examination results of patients with recurrent fever.Nocardia pneumonia is an opportunistic infection.Patients with CD4+T-cell deficiency should be aware of Nocardia infection.展开更多
In this paper,Haar collocation algorithmis developed for the solution of first-order ofHIV infection CD4^(+)T-Cells model.In this technique,the derivative in the nonlinear model is approximated by utilizing Haar funct...In this paper,Haar collocation algorithmis developed for the solution of first-order ofHIV infection CD4^(+)T-Cells model.In this technique,the derivative in the nonlinear model is approximated by utilizing Haar functions.The value of the unknown function is obtained by the process of integration.Error estimation is also discussed,which aims to reduce the error of numerical solutions.The numerical results show that the method is simply applicable.The results are compared with Runge-Kutta technique,Bessel collocation technique,LADM-Pade and Galerkin technique available in the literature.The results show that the Haar technique is easy,precise and effective.展开更多
Background: HIV infection results in depletion of immunocompetent cells such as CD4<sup>+</sup> T-cells. Trace elements such as Copper, Zinc and selenium are known to be involved in immune function. In rec...Background: HIV infection results in depletion of immunocompetent cells such as CD4<sup>+</sup> T-cells. Trace elements such as Copper, Zinc and selenium are known to be involved in immune function. In recent times, HIV-positive patients are treated with antiretroviral therapy (ART), with significant progress. This study was aimed at evaluating CD4<sup>+</sup> T-cells levels, serum Copper, Zinc and Selenium levels in HIV seropositive subjects on ART and ART naive subjects (HIV positive subjects that have not started ART treatment) in Rivers State, Nigeria. Methods: 150 subjects aged 20 to 79 years were recruited after informed consent. 70 subjects were HIV-positive on ART, 30 subjects were HIV-positive ART naïve subjects, while 50 subjects were apparently healthy subjects. Ten (10) milliliters of blood was collected using a standard venipuncture technique from each subject for the analysis of CD4 T-cells using BD fluorescent activated cell sorter (FACSC count), serum Copper and Zinc were analyzed colorimetrically using semi auto-analyzer WP 21E, while selenium was analyzed using atomic absorption spectrophotometer ELICO, SL173. Data generated were analyzed using Graph-Pad Prism version 8.0.2 and p Result: This study revealed a significant reduction in mean zinc, selenium and CD4<sup>+</sup> T-cell level respectively (p = 0.0006;0.0001;0.0001) in HIV-Positive subjects on ART and ART naive. There was also a significant increase in mean serum copper level in the HIV-positive subject as compared to control subjects (p = 0.0001). ART treatment improved the CD4<sup>+</sup> T cell count and serum levels of selenium and zinc;however, ART did not correct the imbalance. Furthermore, female subjects on ART have a significantly higher CD4<sup>+</sup> T-cell count than the males (p Conclusion: Selenium and Zinc deficiency are associated with HIV disease despite the role of ART hence micronutrient supplementation is advised for HIV-positive subjects on ART.展开更多
CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s...CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.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
The proportion and changes of CD4^+CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral bloo...The proportion and changes of CD4^+CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3^+, CD4^+ and CD8^+) and CD4^+CD25^high Tr cells. The results showed that the proportion of CD4^+CD25^high Tr cells in NSCLC group was significantly higher than in control group [(4.36 ±2.07) % vs (2.04±1.03) %, P〈0.01]. The proportion of CD4^+CD25^ high Tr cells in late stage was higher than that in early stage [stages Ⅰ +Ⅱ (2.264±0.6) %; stage Ⅲ(3.284± 1.38) %; stage IV (6.06 4±4.08) %] (P〈0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4^+CD25^high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4^+CD25^high Tr cells in peripheral blood may be related to im- munosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4^+CD25^high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4^+CD25^high Tr cell therapy to treat NSCLC patients may be an effective strategy.展开更多
CD4 expression is rare in diffuse large B-cell lymphoma(DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell ly...CD4 expression is rare in diffuse large B-cell lymphoma(DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20(5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved(67%). Patients received chemotherapy +/- radiation(6/6) and bone marrow transplant(2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively.展开更多
Background:Among HlV-infected patients initiating antiretroviral therapy (ART),early changes in CD4+ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a subop...Background:Among HlV-infected patients initiating antiretroviral therapy (ART),early changes in CD4+ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4+ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods:Thirty-one adult patients with baseline CD4+ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results:Median baseline CD4+ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation:a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4+ T-cell count 〉200 cells/ mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs.27.3% respectively;P =0.017) and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907),and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions:Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.展开更多
CD4^+ T-cell help (CD4 help) plays a pivotal role in CD8^+ T-cell responses against viral infections. However, the role in primary CD8^+ T-cell responses remains controversial. We evaluated the effects of infecti...CD4^+ T-cell help (CD4 help) plays a pivotal role in CD8^+ T-cell responses against viral infections. However, the role in primary CD8^+ T-cell responses remains controversial. We evaluated the effects of infection route and viral dose on primary CD8^+ T-cell responses to vaccinia virus (VACV) in MHC class II^-/- mice. CD4 help deficiency diminished the generation of VACV-specific CD8^+ T cells after intraperitoneal (i.p.) but not after intranasal (i.n.) infection. A large viral dose could not restore normal expansion of VACV-specific CD8^+ T cells in i.p. infected MHC II-/- mice. In contrast, dependence on CD4 help was observed in i.n. infected MHC II-/- mice when a small viral dose was used. These data suggested that primary CD8~ T-cell responses are less dependent on CD4 help in i.n. infection compared to i.p. infection. Activated CD8~ T cells produced more I FN-y, TNF-a and granzyme B in i.n. infected mice than those in i.p. infected mice, regardless of CD4 help. IL-2 signaling via CD25 was not necessary to drive expansion of VACV-specific CD8~ T cells in i.n. infection, but it was crucial in i.p. infection. VACV-specific CD8^+ T cells underwent increased apoptosis in the absence of CD4 help, but proliferated normally and had cytotoxic potential, regardless of infection route. Our results indicate that route of infection and viral dose are two determinants for CD4 help dependence, and intranasal infection induces more potent effector CD8^+ T cells than i.D. infection.展开更多
With the support by the National Natural Science Foundation of China,the research team directed by Prof.Huang HeFeng(黄荷风)at Shanghai Key Laboratory of Embryo Original Disease,Institute of Embryo Fetal Original Adul...With the support by the National Natural Science Foundation of China,the research team directed by Prof.Huang HeFeng(黄荷风)at Shanghai Key Laboratory of Embryo Original Disease,Institute of Embryo Fetal Original Adult Disease and International Peace Maternity&.Child Health Hospital,School of Medicine,Shanghai Jiao Tong University.展开更多
The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein poly...The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein polynomials (OBPs). By applying the proposed method, the nonlinear system of ordinary differential equations reduces to a nonlinear system of algebraic equations which can be solved by using a suitable numerical method such as Newton's method. We prove some useful theorems concerning the convergence and error estimate associated to the present method. Finally, we apply the proposed method to get the numerical solution of this model with the arbitrary initial conditions and values. Furthermore, the numerical results obtained by the suggested method are compared with the results achieved by other previous methods. These results indicate that this method agrees with other previous methods.展开更多
In this paper, the human immunodeficiency virus (HIV) infection model of CD4+ T-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construc...In this paper, the human immunodeficiency virus (HIV) infection model of CD4+ T-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construct the operational matrix of integration for bases of Taylor polynomials. Then, by using this matrix operation and approximation by polynomials, the HIV infection problem is transformed into a system of algebraic equations, whose roots are used to determine the approximate solutions. An important feature of the method is that it does not require collocation points. In addition, an error estimation technique is presented. We apply the present method to two numerical examples and compare our results with other methods.展开更多
A murine CD4+ thymocyte subset with phenotype of TCRαβ + 3G11- 6C10- CD4 + CD8- CD69 + /- HSAmed/lo contains the cells in relatively functional matured status. The functional property of the cells in this subset is ...A murine CD4+ thymocyte subset with phenotype of TCRαβ + 3G11- 6C10- CD4 + CD8- CD69 + /- HSAmed/lo contains the cells in relatively functional matured status. The functional property of the cells in this subset is characterized by the unique pattern of cytokine production at transitional stage from ThO to Th2 type with the latter being the dominant type. After being co-cultured with murine thymic medullary epithelial cell line (MTEC1) cells, a murine展开更多
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BACKGROUND Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms,but the treatment and anti-infective medication are completely different.Here,we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica(N.cyriacigeorgica),which was misdiagnosed as community-acquired pneumonia(CAP)with repeated fever.CASE SUMMARY A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months.After the anti-infection treatment failed in the local hospital,the patient came to our hospital for further treatment.Enhanced computed tomography showed multiple patchy,nodular and strip-shaped high-density shadows in both lungs.A routine haematological examination was performed and showed abnormalities in CD19+B cells and CD4+T cells.Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope,which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N.cyriacigeorgica.The patient’s condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day.CONCLUSION The antibiotic treatment of Nocardia pneumonia is different from that of common CAP.Attention should be given to the pathogenic examination results of patients with recurrent fever.Nocardia pneumonia is an opportunistic infection.Patients with CD4+T-cell deficiency should be aware of Nocardia infection.
文摘In this paper,Haar collocation algorithmis developed for the solution of first-order ofHIV infection CD4^(+)T-Cells model.In this technique,the derivative in the nonlinear model is approximated by utilizing Haar functions.The value of the unknown function is obtained by the process of integration.Error estimation is also discussed,which aims to reduce the error of numerical solutions.The numerical results show that the method is simply applicable.The results are compared with Runge-Kutta technique,Bessel collocation technique,LADM-Pade and Galerkin technique available in the literature.The results show that the Haar technique is easy,precise and effective.
文摘Background: HIV infection results in depletion of immunocompetent cells such as CD4<sup>+</sup> T-cells. Trace elements such as Copper, Zinc and selenium are known to be involved in immune function. In recent times, HIV-positive patients are treated with antiretroviral therapy (ART), with significant progress. This study was aimed at evaluating CD4<sup>+</sup> T-cells levels, serum Copper, Zinc and Selenium levels in HIV seropositive subjects on ART and ART naive subjects (HIV positive subjects that have not started ART treatment) in Rivers State, Nigeria. Methods: 150 subjects aged 20 to 79 years were recruited after informed consent. 70 subjects were HIV-positive on ART, 30 subjects were HIV-positive ART naïve subjects, while 50 subjects were apparently healthy subjects. Ten (10) milliliters of blood was collected using a standard venipuncture technique from each subject for the analysis of CD4 T-cells using BD fluorescent activated cell sorter (FACSC count), serum Copper and Zinc were analyzed colorimetrically using semi auto-analyzer WP 21E, while selenium was analyzed using atomic absorption spectrophotometer ELICO, SL173. Data generated were analyzed using Graph-Pad Prism version 8.0.2 and p Result: This study revealed a significant reduction in mean zinc, selenium and CD4<sup>+</sup> T-cell level respectively (p = 0.0006;0.0001;0.0001) in HIV-Positive subjects on ART and ART naive. There was also a significant increase in mean serum copper level in the HIV-positive subject as compared to control subjects (p = 0.0001). ART treatment improved the CD4<sup>+</sup> T cell count and serum levels of selenium and zinc;however, ART did not correct the imbalance. Furthermore, female subjects on ART have a significantly higher CD4<sup>+</sup> T-cell count than the males (p Conclusion: Selenium and Zinc deficiency are associated with HIV disease despite the role of ART hence micronutrient supplementation is advised for HIV-positive subjects on ART.
文摘CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.
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This project was supported by grants from National Science Fundation for Distinguished Young Scholars (No. 30225038) The National Basic Research Program(No.2001CB5101).
文摘The proportion and changes of CD4^+CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3^+, CD4^+ and CD8^+) and CD4^+CD25^high Tr cells. The results showed that the proportion of CD4^+CD25^high Tr cells in NSCLC group was significantly higher than in control group [(4.36 ±2.07) % vs (2.04±1.03) %, P〈0.01]. The proportion of CD4^+CD25^ high Tr cells in late stage was higher than that in early stage [stages Ⅰ +Ⅱ (2.264±0.6) %; stage Ⅲ(3.284± 1.38) %; stage IV (6.06 4±4.08) %] (P〈0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4^+CD25^high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4^+CD25^high Tr cells in peripheral blood may be related to im- munosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4^+CD25^high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4^+CD25^high Tr cell therapy to treat NSCLC patients may be an effective strategy.
文摘CD4 expression is rare in diffuse large B-cell lymphoma(DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20(5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved(67%). Patients received chemotherapy +/- radiation(6/6) and bone marrow transplant(2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively.
基金This study was supported by the National Natural Science Foundation of China (No. 81071372), the National Key Technologies R and D Program for the 11th Five-year Plan (No. 2008ZX10001-006), the National Key Technologies R and D Program for the 12th Five-year Plan (No. 2012ZX10001003-001), and the Key Clinical Program of the Ministry of Health (2010-2012).
文摘Background:Among HlV-infected patients initiating antiretroviral therapy (ART),early changes in CD4+ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4+ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods:Thirty-one adult patients with baseline CD4+ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results:Median baseline CD4+ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation:a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4+ T-cell count 〉200 cells/ mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs.27.3% respectively;P =0.017) and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907),and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions:Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.
文摘CD4^+ T-cell help (CD4 help) plays a pivotal role in CD8^+ T-cell responses against viral infections. However, the role in primary CD8^+ T-cell responses remains controversial. We evaluated the effects of infection route and viral dose on primary CD8^+ T-cell responses to vaccinia virus (VACV) in MHC class II^-/- mice. CD4 help deficiency diminished the generation of VACV-specific CD8^+ T cells after intraperitoneal (i.p.) but not after intranasal (i.n.) infection. A large viral dose could not restore normal expansion of VACV-specific CD8^+ T cells in i.p. infected MHC II-/- mice. In contrast, dependence on CD4 help was observed in i.n. infected MHC II-/- mice when a small viral dose was used. These data suggested that primary CD8~ T-cell responses are less dependent on CD4 help in i.n. infection compared to i.p. infection. Activated CD8~ T cells produced more I FN-y, TNF-a and granzyme B in i.n. infected mice than those in i.p. infected mice, regardless of CD4 help. IL-2 signaling via CD25 was not necessary to drive expansion of VACV-specific CD8~ T cells in i.n. infection, but it was crucial in i.p. infection. VACV-specific CD8^+ T cells underwent increased apoptosis in the absence of CD4 help, but proliferated normally and had cytotoxic potential, regardless of infection route. Our results indicate that route of infection and viral dose are two determinants for CD4 help dependence, and intranasal infection induces more potent effector CD8^+ T cells than i.D. infection.
文摘With the support by the National Natural Science Foundation of China,the research team directed by Prof.Huang HeFeng(黄荷风)at Shanghai Key Laboratory of Embryo Original Disease,Institute of Embryo Fetal Original Adult Disease and International Peace Maternity&.Child Health Hospital,School of Medicine,Shanghai Jiao Tong University.
文摘The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein polynomials (OBPs). By applying the proposed method, the nonlinear system of ordinary differential equations reduces to a nonlinear system of algebraic equations which can be solved by using a suitable numerical method such as Newton's method. We prove some useful theorems concerning the convergence and error estimate associated to the present method. Finally, we apply the proposed method to get the numerical solution of this model with the arbitrary initial conditions and values. Furthermore, the numerical results obtained by the suggested method are compared with the results achieved by other previous methods. These results indicate that this method agrees with other previous methods.
文摘In this paper, the human immunodeficiency virus (HIV) infection model of CD4+ T-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construct the operational matrix of integration for bases of Taylor polynomials. Then, by using this matrix operation and approximation by polynomials, the HIV infection problem is transformed into a system of algebraic equations, whose roots are used to determine the approximate solutions. An important feature of the method is that it does not require collocation points. In addition, an error estimation technique is presented. We apply the present method to two numerical examples and compare our results with other methods.
文摘A murine CD4+ thymocyte subset with phenotype of TCRαβ + 3G11- 6C10- CD4 + CD8- CD69 + /- HSAmed/lo contains the cells in relatively functional matured status. The functional property of the cells in this subset is characterized by the unique pattern of cytokine production at transitional stage from ThO to Th2 type with the latter being the dominant type. After being co-cultured with murine thymic medullary epithelial cell line (MTEC1) cells, a murine