Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A to...Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.展开更多
Objective: To determine the role of CD4+ and CD8+ T lymphocytes in the onset of stroke in people living with HIV. Methodology: This was a descriptive, cross-sectional study from January to July 2019, in the neurology ...Objective: To determine the role of CD4+ and CD8+ T lymphocytes in the onset of stroke in people living with HIV. Methodology: This was a descriptive, cross-sectional study from January to July 2019, in the neurology department of loandjili general hospital, including any patient hospitalized for a first episode of stroke confirmed by brain scan. The study variables were: age, sex, CRP value, serum T cell CD4+, CD8+. The statistical analysis was carried out using the EPI info 7 software. Results: Twenty stroke patients were included. The relative frequency of HIV was 20%. The risk factors were potentiated by immunosuppression of CD4+ T cells. Sixty percent (60%) of the patients had a CD4+ count < 200/mm<sup>3</sup> and the mean CD4+ count was ±191/mm<sup>3</sup>. Stroke was the predominant mechanism of injury with a frequency of 70%, the only injury mechanism of stroke in patients with CD8+ T cell count > 800/mm<sup>3</sup> (p = 0.04). Conclusion: Risk factors are potentiated by TCD4+ lymphocyte immunosupression, also CD8+ lymphocytes of immune system activation marker are a cardiovascular risk factor for living people with HIV.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
Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to ex...Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.展开更多
BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study eval...BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.展开更多
Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy people...Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.展开更多
T淋巴细胞在抗肿瘤免疫中发挥重要作用。根据细胞表面CD分子的不同,T细胞可分为CD4+T细胞和CD8+T细胞。CD4+T细胞活化后的主要效应细胞为辅助性T细胞(help T lymphocyte,Th),CD8+T细胞活化后的主要效应细胞为细胞毒性T细胞(cy...T淋巴细胞在抗肿瘤免疫中发挥重要作用。根据细胞表面CD分子的不同,T细胞可分为CD4+T细胞和CD8+T细胞。CD4+T细胞活化后的主要效应细胞为辅助性T细胞(help T lymphocyte,Th),CD8+T细胞活化后的主要效应细胞为细胞毒性T细胞(cytotoxicTlymphocyte,CTL)。CTL对肿瘤细胞起直接杀伤作用。Th对CTL的免疫活性起调节和促进作用。展开更多
CD8^(+) T lymphocytes are pivotal cells in the host response to antitumor immunity.Tumordriven microenvironments provide the conditions necessary for regulating infiltrating CD8^(+) T cells in favor of tumor survival,...CD8^(+) T lymphocytes are pivotal cells in the host response to antitumor immunity.Tumordriven microenvironments provide the conditions necessary for regulating infiltrating CD8^(+) T cells in favor of tumor survival,including weakening CD8^(+) T cell activation,driving tumor cells to impair immune attack,and recruiting other cells to reprogram the immune milieu.Also in tumor microenvironment,stromal cells exert immunosuppressive skills to avoid CD8^(+) T cell cytotoxicity.In this review,we explore the universal function and fate decision of infiltrated CD8^(+) T cells and highlight their antitumor response within various stromal architectures in the process of confronting neoantigen-specific tumor cells.Thus,this review provides a foundation for the development of antitumor therapy based on CD8^(+)T lymphocyte manipulation.展开更多
Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus ha...Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.展开更多
THE T cell repertoire is characterized by an extremely diverse population of different surface receptors (TCR) which participates in highly specific responses to a large number of different antigens and mediate antige...THE T cell repertoire is characterized by an extremely diverse population of different surface receptors (TCR) which participates in highly specific responses to a large number of different antigens and mediate antigen stimulation signals. Variable heterodimers of TCR α/β and γ/δ receptors are associated with invariable CD3γ, δ, ε and ζ proteins, thus forming the TCR/CD3 complex. CD3ε plays an important role in the initiation of TCR resembling and signfal transduction among the octopeptide chains. Stimulation by anti-CD3ε monoclonal展开更多
Objective To investigate melatonin-related mechanisms of action on immunoregulation in aged and immunodeficient mice. Methods T lymPhocytes subunit CD4 + ,CD8 + and CD4 + /CD8 + ratio were measured...Objective To investigate melatonin-related mechanisms of action on immunoregulation in aged and immunodeficient mice. Methods T lymPhocytes subunit CD4 + ,CD8 + and CD4 + /CD8 + ratio were measured by Flow Cytometer in normal, aged and Cyclophosphamide injected mice which treated with melatonin, and compared with the results of T lymphocytes subunit in the group without melatonin as control group. Results The percentage of CD4 + , CD8 + T cells in the normal mice which treated with melatonin was significantly higher than that in control group ( P <0.01), CD4 + /CD8 + ratio was higher but had no significant difference. In the cyclophosphamide injected group which melatonin treated, the percentage of CD4 + T cells and CD4 + /CD8 + ratio were higher than those in control, The difference was significant ( P <0.01), while CD8 + was lower ( P <0.01). In aged melatonin treated mice group, the percentage of CD4 + , CD8 + T cells and CD4 + /CD8 + ratio were significantly higher than those in control ( P <0.01). Conclusion Melatonin could adjust the quantity and the ratio of CD4 + , CD8 + T cells in aged and immunodeficient mice. it implied that melatonin could mediate helper and suppression T lymphocytes to reinforce their immunodefence.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
文摘Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.
文摘Objective: To determine the role of CD4+ and CD8+ T lymphocytes in the onset of stroke in people living with HIV. Methodology: This was a descriptive, cross-sectional study from January to July 2019, in the neurology department of loandjili general hospital, including any patient hospitalized for a first episode of stroke confirmed by brain scan. The study variables were: age, sex, CRP value, serum T cell CD4+, CD8+. The statistical analysis was carried out using the EPI info 7 software. Results: Twenty stroke patients were included. The relative frequency of HIV was 20%. The risk factors were potentiated by immunosuppression of CD4+ T cells. Sixty percent (60%) of the patients had a CD4+ count < 200/mm<sup>3</sup> and the mean CD4+ count was ±191/mm<sup>3</sup>. Stroke was the predominant mechanism of injury with a frequency of 70%, the only injury mechanism of stroke in patients with CD8+ T cell count > 800/mm<sup>3</sup> (p = 0.04). Conclusion: Risk factors are potentiated by TCD4+ lymphocyte immunosupression, also CD8+ lymphocytes of immune system activation marker are a cardiovascular risk factor for living people with HIV.
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.
基金Fund supported by the Healthcare Technology Plan of Zhejiang Provincial Health Bureau(No.2016KYB292)the Technology Plan of Science and Technology Bureau of Jiaxing,Zhejiang province(No.2016AY23054)~~
文摘Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.
文摘BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.
基金supported by the National Natural Science Foundation of China(No.81602020).
文摘Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.
文摘T淋巴细胞在抗肿瘤免疫中发挥重要作用。根据细胞表面CD分子的不同,T细胞可分为CD4+T细胞和CD8+T细胞。CD4+T细胞活化后的主要效应细胞为辅助性T细胞(help T lymphocyte,Th),CD8+T细胞活化后的主要效应细胞为细胞毒性T细胞(cytotoxicTlymphocyte,CTL)。CTL对肿瘤细胞起直接杀伤作用。Th对CTL的免疫活性起调节和促进作用。
基金supported by the Strategic Priority Research Program of the Chinese Academy of Science (No. XDA12020101, China)the National Natural Science Foundation of China (81773763)。
文摘CD8^(+) T lymphocytes are pivotal cells in the host response to antitumor immunity.Tumordriven microenvironments provide the conditions necessary for regulating infiltrating CD8^(+) T cells in favor of tumor survival,including weakening CD8^(+) T cell activation,driving tumor cells to impair immune attack,and recruiting other cells to reprogram the immune milieu.Also in tumor microenvironment,stromal cells exert immunosuppressive skills to avoid CD8^(+) T cell cytotoxicity.In this review,we explore the universal function and fate decision of infiltrated CD8^(+) T cells and highlight their antitumor response within various stromal architectures in the process of confronting neoantigen-specific tumor cells.Thus,this review provides a foundation for the development of antitumor therapy based on CD8^(+)T lymphocyte manipulation.
文摘Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.
文摘THE T cell repertoire is characterized by an extremely diverse population of different surface receptors (TCR) which participates in highly specific responses to a large number of different antigens and mediate antigen stimulation signals. Variable heterodimers of TCR α/β and γ/δ receptors are associated with invariable CD3γ, δ, ε and ζ proteins, thus forming the TCR/CD3 complex. CD3ε plays an important role in the initiation of TCR resembling and signfal transduction among the octopeptide chains. Stimulation by anti-CD3ε monoclonal
文摘Objective To investigate melatonin-related mechanisms of action on immunoregulation in aged and immunodeficient mice. Methods T lymPhocytes subunit CD4 + ,CD8 + and CD4 + /CD8 + ratio were measured by Flow Cytometer in normal, aged and Cyclophosphamide injected mice which treated with melatonin, and compared with the results of T lymphocytes subunit in the group without melatonin as control group. Results The percentage of CD4 + , CD8 + T cells in the normal mice which treated with melatonin was significantly higher than that in control group ( P <0.01), CD4 + /CD8 + ratio was higher but had no significant difference. In the cyclophosphamide injected group which melatonin treated, the percentage of CD4 + T cells and CD4 + /CD8 + ratio were higher than those in control, The difference was significant ( P <0.01), while CD8 + was lower ( P <0.01). In aged melatonin treated mice group, the percentage of CD4 + , CD8 + T cells and CD4 + /CD8 + ratio were significantly higher than those in control ( P <0.01). Conclusion Melatonin could adjust the quantity and the ratio of CD4 + , CD8 + T cells in aged and immunodeficient mice. it implied that melatonin could mediate helper and suppression T lymphocytes to reinforce their immunodefence.