急性冠脉综合征患者CD4~+T淋巴细胞亚群的变化及临床意义

目的:研究急性冠脉综合征(ACS)患者CD4+T淋巴细胞亚群的变化及临床意义。方法:收集2013年3月-2014年3月入住我院首次行冠脉成形术(PCI)治疗的ACS患者88例以及造影结果正常患者28例。分别于冠脉造影时取冠脉血流式细胞技术检测CD4+T细胞亚群Th1/Th2、Th17/Treg比例表达变化。结果:与对照组相比,ACS组患者冠脉血中Th1、Th17细胞占CD4+T淋巴细胞的百分比显著升高,而Th1、Treg细胞占CD4+T淋巴细胞的百分比显著降低,差异具有统计学意义(P0.05)。结论:ACS患者体内免疫反应增强,CD4+T淋巴细胞不同功能亚群均参与了动脉粥样硬化(AS)的发生发展,Th1、Th17可促进AS的进展和不稳定性,而Th1、Treg作用相反。     

CD8+T淋巴细胞与高血压心肌纤维化的研究进展

血管生长因子增多,血管平滑肌细胞增殖和炎症在血管重塑方面起到了关键的作用。这种低级的炎症反应导致粘附分子表达,白细胞的侵入,细胞因子的产生,氧化应激的增加,从而激活免疫细胞和血管炎症信号通路,使T淋巴细胞及巨噬细胞等细胞活化,产生和释放多种活性因子,激活心肌的细胞外基质生成细胞,引起胶原形成及代谢异常,并可导致心肌实质细胞的变性、坏死或亚细胞结构变化等,从而引起心肌纤维化一系列病理生理变化。本文主要就CD8+T淋巴细胞在高血压心肌纤维化炎症反应中的细胞毒性作用、诱导细胞凋亡作用、分泌大量的炎症因子、增加MMPs的活性从而影响心肌纤维化的形成等方面做一综述!     

A retrospective evaluation of the role of T cells in the development of malaria vaccine

Due to the fact that the life cycle of malaria parasites is complex, undergoing both an extracellular and intracellular phases in its host, the human immune system has to mobilize both the humoral and cellular arms of immune responses to fight against this parasitic infection. Whereas humoral immunity is directed toward the extracellular stages which include sporozoites and merozoites, cell-mediated immunity (CMI), in which T cells play a major role, targets hepatic stages - liver stages - of the parasites. In this review, the role of T cells in protective immunity against liver stages of the malaria infection is being re-evaluated. Furthermore, this review intends to address how to translate the findings regarding the role of T cells obtained in experimental systems to actual development of malaria vaccine for humans.     

Increased glucocorticoid responsiveness of CD4+ T-cell clonal lines grown in serum-free media

Summary CEM-C7, a human leukemic CD4+ T-lymphocyte cell line and three of its subclones, CEM-4R4, CEM-3R43, and ICR-27, previously cultured in a medium supplemented with 5 to 10% fetal bovine serum, have been adapted to serum-free media. The best medium of those tested was RPMI 1640 supplemented with 5 μg/ml each transferrin and insulin + 5 ng/ml sodium selinite ± 0.1% bovine serum albumin. While growing either with or without albumin, the several clonal lines of CEM cells displayed growth similar to serum-supplemented cultures. Cell proliferation of CEM-C7 cells cultured in both serum-free media has been sustained for 3 mo, with culture doubling times of about 25 h for both serum-supplemented and serum-free cultures (viability ≥ 90%). Cell morphology remained essentially the same in serum-free or serum containing media. The expression of CD4, a marker for T-derived lymphoid cells, was not significantly different in serum-free medium. When grown in serum-free medium, CEM-C7 cells exhibited increased steroid responsiveness as evidenced by increased glucocorticoid receptor binding sites, increased induction of glutamine synthetase, and cell lysis at lower concentrations of steroid. Receptor mutant subclones of CEM-C7, which are proven to be completely unresponsive to micromolar concentrations of dexamethasone when grown in serum-supplemented medium, become partially sensitive to the hormone after growth in defined medium. The increased sensitivity of CEM-C7 cells and its subclones to dexamethasone in serum-free medium returned to previous levels when these cells were recultured in serum-containing medium. Our results suggest that substances in serum influence steroid effects on these cells and that the molecular details of glucocorticoid hormone action may be pursued more precisely in a clearly defined culture medium. This work was conducted in conjunction with the Walls Medical Research Foundation.     

Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine

Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-γ secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (T_reg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ T_reg cells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine. J.-Y. Liu and Y. Wu contributed equally to this work.     

Ability of CD8(+) T cell anti-feline immunodeficiency virus activity correlated with peripheral CD4(+) T cell counts and plasma viremia

In the host defense mechanism against feline immunodeficiency virus (FIV) infection, CD8(+) T cells specifically attack virus-infected cells and suppress the replication of the virus in a non-cytolytic manner by secreting soluble factors. In this study, we measured CD8(+) T cell anti-FIV activity in 30 FIV-infected cats. We investigated its relationship with the number of peripheral blood lymphocytes, particularly the CD4(+) T cell and CD8(+) T cell counts, and the relationship between anti-FIV activity and the number of T cells of CD8alpha(+)beta(lo) and CD8alpha(+)beta(-) phenotypes. A clearly significant correlation was observed between anti-FIV activity and the number of CD4(+) T cells. A weaker anti-FIV activity was associated with a greater decrease in the number of CD4(+) T cells. However, there was no significant correlation between anti-FIV activity and the number of B or CD8(+) T cells. Compared with SPF cats, FIV-infected cats had significantly higher CD8alpha(+)beta(lo) T cell and CD8alpha(+)beta(-) T cell counts, but, no significant correlation was observed between these cell counts and anti-FIV activity. This anti-FIV activity significantly correlated with plasma viremia, which was detected in cats with a weak anti-FIV activity. These results suggest that the anti-FIV activity of CD8(+) T cells plays an important role in plasma viremia and the maintenance of CD4(+) T cells in the body. It is unlikely that CD8alpha(+)beta(lo) or CD8alpha(+)beta(-) T cells appearing after FIV infection represent a phenotype of CD8(+) cells with anti-FIV activity.     

Regulatory T cells constrain the TCR repertoire of antigen‐stimulated conventional CD4 T cells

To analyze the potential role of Tregs in controlling the TCR repertoire breadth to a non‐self‐antigen, a TCRβ transgenic mouse model (EF4.1) expressing a limited, yet polyclonal naïve T‐cell repertoire was used. The response of EF4.1 mice to an I‐Ab‐associated epitope of the F‐MuLV envelope protein is dominated by clones expressing a Vα2 gene segment, thus allowing a comprehensive analysis of the TCRα repertoire in a relatively large cohort of mice. Control and Treg‐depleted EF4.1 mice were immunized, and the extent of the Vα2‐bearing, antigen‐specific TCR repertoire was characterized by high‐throughput sequencing and spectratyping analysis. In addition to increased clonal expansion and acquisition of effector functions, Treg depletion led to the expression of a more diverse TCR repertoire comprising several private clonotypes rarely observed in control mice or in the pre‐immune repertoire. Injection of anti‐CD86 antibodies in vivo led to a strong reduction in TCR diversity, suggesting that Tregs may influence TCR repertoire diversity by modulating costimulatory molecule availability. Collectively, these studies illustrate an additional mechanism whereby Tregs control the immune response to non‐self‐antigens.     

敲低肿瘤细胞来源的颗粒体蛋白前体抑制C57BL/6J小鼠黑色素移植瘤的生长

颗粒体蛋白前体 (progranulin, PGRN)在多种肿瘤中过表达。但PGRN在黑色素瘤发生发展中的作用尚无报道。为探究PGRN在黑色素肿瘤中的作用,本研究采用CRISPR-Cas9基因编辑技术建立了稳定敲低PGRN的小鼠黑色素瘤B16细胞株B16-PGRNlow。MTS法和BrdU掺入结合流式细胞（计量）术分析证明,敲低PGRN不影响B16细胞的细胞周期和增殖。将B16-ctrl（对照）和B16-PGRNlow细胞分别皮下接种野生型（WT）和PGRN敲除（KO）的C57BL/6J小鼠,比较观察黑色素移植瘤体积大小。移植瘤形成20 d后,与B16-ctrl细胞接种的移植瘤比较,无论在WT还是在KO荷瘤小鼠,B16-PGRNlow形成的移植瘤体积明显减小（WT鼠：P<0.05;KO鼠：P<0.01）。然而,比较B16-PGRNlow或B16-ctrl在WT鼠与KO鼠形成的移植瘤体积大小,并无显著差异,提示B16肿瘤细胞PGRN而非宿主PGRN影响移植瘤的生长。流式细胞术分析显示,在荷B16-PGRNlow移植瘤的WT型小鼠脾和淋巴结中,CD4+、CD8+T细胞数（百分比）比荷B16-ctrl移植瘤的WT鼠脾和淋巴结的CD4+、CD8+T细胞数明显增多（P<0.05,P<0.01）,而在KO鼠却未见明显差异。上述结果证明,敲低肿瘤细胞PGRN可抑制黑色素移植瘤的生长。上述结果还提示,抑制PGRN在黑色瘤的表达可引起脾和淋巴结CD4+和CD8+T细胞增加,提高宿主的细胞免疫能力。其机制尚待进一步研究。本文的发现为PGRN作为黑色素瘤治疗的潜在靶点提供了新证据。     

应用流式细胞术分析林麝外周血 CD4+、CD8+ T淋巴细胞

通过对圈养林麝(Moschusberezovskii)外周血淋巴细胞CD4~+、CD8~+亚群的检测,探讨林麝细胞免疫功能状态,并探索应用流式细胞仪分析其淋巴细胞亚群的方法,为研究林麝重大疾病的病理机制及诊断方法提供科学依据。本研究选取健康林麝和患呼吸道疾病林麝各5头,以双色流式细胞术检测其外周血淋巴细胞CD4~+、CD8~+亚群的含量,并进行比较。结果显示,羊源CD4、CD8的流式荧光抗体能够标记林麝细胞并有效检测;患病林麝与健康林麝相比,外周血CD4~+细胞含量无差异(P 0.05),CD8~+细胞含量则显著降低(P 0.01),CD4~+/CD8~+比值显著增高(P 0.01)。结果表明,患呼吸系统炎性疾病的林麝其外周血淋巴细胞CD8~+亚群变化显著,检测淋巴细胞亚群对林麝疾病的诊断有重要意义。     

Genetic approaches for the induction of a CD4+ T cell response in cancer immunotherapy

Recently, it has become more and more obvious that not only CD8+ cytotoxic T lymphocytes, but also CD4+ T helper cells are required for the induction of an optimal, long-lasting anti-tumor immune response. CD4+ T helper cells, and in particular IFN-gamma-secreting type 1 T helper cells, have been shown to fulfill a critical function in the mounting of a cancer-specific response. Consequently, targeting antigens into MHC class II molecules would greatly enhance the efficacy of an anti-cancer vaccine. The dissection of the MHC class II presentation pathway has paved the way for rational approaches to achieve this goal: novel systems have been developed to genetically manipulate the MHC class II presentation pathway. First, different genetic approaches have been used for the delivery of known epitopes into the MHC class II processing pathway or directly onto the peptide-binding groove of the MHC molecules. Second, several strategies exist for the targeting of whole tumor antigens, containing both MHC class I and class II restricted epitopes, to the MHC class II processing pathway. We review these data and describe how this knowledge is currently applied in vaccine development.     

Traffic of proteins and peptides across membranes for immunosurveillance by CD8(+) T lymphocytes: a topological challenge

Cytotoxic CD8(+) T lymphocytes kill infected cells that display major histocompatibility complex (MHC) class I molecules presenting peptides processed from pathogen proteins. In general, the peptides are proteolytically processed from newly made endogenous antigens in the cytosol and require translocation to the endoplasmic reticulum (ER) for MHC class I loading. This last task is performed by the transporters associated with antigen processing (TAP). Sampling of suspicious pathogen-derived proteins reaches beyond the cytosol, and MHC class I loading can occur in other secretory or endosomal compartments besides the ER. Peptides processed from exogenous antigens can also be presented by MHC class I molecules to CD8(+) T lymphocytes, in this case requiring delivery from the extracellular medium to the processing and MHC class I loading compartments. The endogenous or exogenous antigen can be processed before or after its transport to the site of MHC class I loading. Therefore, mechanisms that allow the full-length protein or processed peptides to cross several subcellular membranes are essential. This review deals with the different intracellular pathways that allow the traffic of antigens to compartments proficient in processing and loading of MHC class I molecules for presentation to CD8(+) T lymphocytes and highlights the need to molecularly identify the transporters involved.     

Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF β 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n = 14) and progressive infection (n = 47), plasma levels of active TGF β 1, INF-γ, TNF-α, IL-10, IL-1β, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n = 12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF β 1 and IL-10 were significantly decreased while IL-1β, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF β 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1β, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.     

HCV-specific interleukin-21+CD4+ T cells responses associated with viral control through the modulation of HCV-specific CD8+ T cells function in chronic hepatitis C patients

Interleukin-21 (IL-21)+CD4+ T cells are involved in the immune response against hepatitis B virus (HBV) by secreting IL-21. However, the role of IL-21+CD4+ T cells in the immune response against chronic hepatitis C (CHC) virus infection is poorly understood. This study aimed to investigate the role of IL-21+CD4+ T cells in CHC patients and the potential mechanisms. The study subjects included nineteen CHC patients who were grouped by viral load (low, < 10⁶ RNA copies/ml, n = 8; high, > 10⁶ RNA copies/ml, n = 11). The peripheral frequency of HCV-specific IL-21+CD4+ T cells was higher in the low viral load group and was negatively correlated with the serum HCV RNA viral load in all CHC patients. Meanwhile, IL-21+ cells accumulated in the liver in the low viral load group. In vitro, IL-21 treatment increased the expression of proliferation markers and cytolytic molecules on HCV-specific CD8+ T cells. In summary, these findings suggest that HCV-specific IL-21+CD4+ T cells might contribute to HCV control by rescuing HCV-specific CD8+ T cells in CHC patients.     

唾液酸免疫球蛋白型凝集素-15促进结直肠癌细胞增殖和迁移并抑制肿瘤组织中CD4+与CD8+T细胞浸润

唾液酸免疫球蛋白型凝集素-15(sialic acid-binding immunoglobulin-type lectin-15,Siglec-15)属于Siglecs家族的一员,是一种新型免疫抑制分子。Siglec-15在多种人类肿瘤细胞和肿瘤相关巨噬细胞中高表达,但Siglec-15在结直肠癌(colorectal cancer,CRC)中的生物学功能及其对免疫微环境的影响尚不明确。本文旨在分析Siglec-15异常表达对CRC细胞功能及CD4⁺T细胞、CD8⁺T细胞浸润的影响。首先,分析TCGA数据库中结直肠癌与正常组织中Siglec-15 mRNA表达水平,并对52例人CRC与配对癌旁组织进行免疫组织化学染色(IHC),发现Siglec-15在CRC中的表达水平高于癌旁组织(P<0.01)。CCK8和划痕愈合结果显示,敲低Siglec-15能抑制人CRC细胞SW480增殖(P<0.01)和迁移(P<0.05)。磁珠分选小鼠脾的CD8⁺T细胞并与小鼠CRC细胞MC38共培养,发现MC38细胞过表达Siglec-15能抑制CD8⁺T细胞对其的杀伤以及IFN-γ和TNF-α的分泌(P<0.01)。小鼠荷瘤结果表明,过表达Siglec-15可以促进小鼠肿瘤生长(P<0.05)。单样本基因集富集分析、荷瘤小鼠肿瘤组织及人结直肠癌组织IHC分析均表明,Siglec-15高表达时,肿瘤微环境中CD4⁺T细胞、CD8⁺T细胞浸润减少(P<0.05)。综上所述,Siglec-15可能通过促进CRC细胞增殖迁移以及抑制CD4⁺T细胞、CD8⁺T细胞浸润促进结直肠癌进展。本文为探究Siglec-15在CRC中的免疫抑制作用提供了一些新的实验依据。     

孟鲁司特钠对哮喘患儿T淋巴细胞亚群CD4~+和CD8~+水平的影响

目的:探讨孟鲁司特钠联合抗生素对哮喘患儿T淋巴细胞亚群CD4+和CD8+水平的影响。方法:选取我院收治的哮喘患儿50例,并将其随机分为两组,每组各25例。对照组予常规抗生素治疗,实验组在此基础上加用孟鲁司特钠治疗。观察和比较两组患儿的临床疗效、一年内复发率,以及CD4+、CD8+和CD4+/CD8+比值的变化情况。结果:两组哮鸣音、咳嗽及喘憋持续时间均获得改善,实验组优于对照组,差异有统计学意义(P0.05)。与同组治疗1天后比较,两组患儿治疗5、10天后的CD4+、CD8+以及CD4+/CD8+比值均明显升高;与同组治疗5天后比较,两组患儿治疗10天后CD4+、CD8+以及CD4+/CD8+比值均明显升高;实验组患儿治疗5天、10天后的CD4+、CD8+以及CD4+/CD8+比值均明显高于对照组,差异均有统计学意义(P0.05)。两组治疗后CD4+、CD8+以及CD4+/CD8+比值变化呈显著差异(P0.05)。实验组1年复发率显著低于对照组,差异有统计学意义(P0.05)。结论:孟鲁司特钠可能通过影响哮喘患儿CD4+、CD8+及CD4+/CD8+水平,改善患儿的临床症状,缩短其住院时间,值得临床推广应用。     

Early hematologic changes in rhesus macaques (Macaca mulatta) infected with pathogenic and nonpathogenic isolates of SIVmac

Early hematologic changes were studied over a 14 day period in three groups of six rhesus macaques intravenously infected with pathogenic and nonpathogenic isolates of SIVmac. Abnormalities in blood included a mild blood loss anemia, sporadic lymphopenia, and variable CD4+ and CD8 + T lymphocyte numbers. Prominent bone marrow findings in macaques inoculated with pathogenic uncloned SIVmac and molecularly cloned pathogenic SIVmac-239 were hypercellularity, myeloid and megakaryocytic hyperplasia, and lymphoid aggregates. Infrequent mild morphologic abnormalities were present in macaques infected with a nonpathogenic molecular clone, SIVmac-1A11.     

HIV/AIDS患者机会性感染与CD4+ T淋巴细胞间的关联性

目的 研究人免疫缺陷病毒（HIV）感染者及艾滋病（AIDS）患者发生机会性感染的概率与自身CD4+ T淋巴细胞之间的关系,为HIV患者机会性感染的防治提供参考。方法 以2016年6月至2017年6月我院400例HIV患者为研究对象,回顾性分析不同CD4+T淋巴细胞计数HIV患者发生机会性感染的情况。结果 400例HIV患者发生机会性感染178例,总感染率为44.5%。CD4+T淋巴细胞计数≤50个/μL的患者机会性感染发生率（86.67%）最高,与其他各组比较差异有统计学意义（P<0.05）。随着CD4+ T淋巴细胞计数的减少,HIV患者机会性感染率升高。178例机会性感染者中,单一感染82例,2部位感染52例,3部位感染28例,4部位以上感染16例。感染病原体检测显示,细菌感染84例（47.19%）,结核杆菌感染36例（20.22%）,病毒感染30例（16.85%,包括巨细胞病毒感染18例、单纯疱疹病毒感染12例）,真菌感染77例（43.25%,包括假丝酵母感染35例,肺孢子菌感染20例,马尔尼菲青霉菌感染12例,新型隐球菌感染10例）,未明确病原体性质34例（19.10%）,复合感染多见。结论 CD4+ T淋巴细胞水平与HIV患者继发机会性感染的概率关系密切。HIV患者CD4+ T淋巴细胞水平的监测对其继发机会性感染的防控具有重要临床意义。     

阿昔洛韦对传染性单核细胞增多患儿CD~(4+)和CD~(8+)的影响

目的:探究阿昔洛韦对小儿传染性单核细胞增多症CD4+、CD8+的影响。方法:选取我院收治的小儿传染性单核细胞增多症的患者64例,随机分为两组。实验组予阿昔洛韦静脉滴注,对照组予利巴韦林静脉滴注。对比两组的临床疗效及CD4+、CD8+和CD4+/CD8+比值的变化情况。结果:1治疗后两组患儿临床疗效,实验组较对照组显著改善,差异有统计学意义(P0.05)。2治疗后两组患儿退热时间、淋巴结消退时间、异型淋巴细胞消失时间以及住院时间等比较,实验组明显较对照组短,差异有统计学意义(P0.05)。3治疗前,两组患者CD4+、CD8+以及CD4+/CD8+比值无统计学差异(P0.05);治疗后,患者CD4+及CD4+/CD8+比值呈现先升高再降低的趋势,CD8+则呈现下降趋势,与对照组比较,实验组治疗3天,10天及1个月CD4+以及CD8+下降明显,差异具有统计学意义(P0.05);CD4+/CD8+比值则较对照组升高(P0.05)。结论:采用阿昔洛韦能够更好的改善患者临床症状,影响CD4+、CD8+的变化,使紊乱的免疫系统较快的恢复。     

Influences of blood sampling procedures on basal hypothalamic-pituitary-adrenal hormone levels and leukocyte values in rhesus macaques (Macaca mulatta)

Abstract: The influences of housing location and temporal factors on the results of blood sampling were examined to determine their contributions to levels of hypothalamic-pituitary-adrenal hormones, as well as leukocyte subset counts from peripheral blood in rhesus monkeys. Differences in housing location and the amount of room disturbance associated with blood sampling have a significant impact on cell counts, but not on ACTH or Cortisol levels.     

Decreased regulatory T‐cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo

The aim of present study was to evaluate CD4⁺/CD8⁺ ratio and CD4⁺CD25^hiFoxP3⁺ Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4⁺/CD8⁺ ratio and Tregs in 82 patients and 50 controls. CD8⁺ T‐cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8⁺ T‐cell counts compared with stable GV patients (p = 0.001). The CD4⁺/CD8⁺ ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4⁺/CD8⁺ ratio and natural Tregs in frequency and function might be involved in the T‐cell mediated pathogenesis of GV and its progression.