T Helper Cells Profile and CD4+CD25+Foxp3+Regulatory T Cells in Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is considered as the most common cause of female infertility that affects 4-10% of women in the reproductive age. Previous studies have shown the role of a balanced immune response in a successful pregnancy and fertility. Objective: To investigate the T helper cells type 1 (Th1) /Th2/Th17/Treg paradigms in peripheral blood of infertile PCOS compared with normal fertile women. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated at the late follicular phase from 10 PCOS and 10 fertile women. PBMCs were stimulated with PMA and ionomycin in the presence of Berefeldin A as Golgi stop agent to detect intracellular cytokine production (IFN-γ, IL-17, and IL-4) from CD3+CD4+T cells population indicating T helper (Th) cells subsets by flowcytometry. Moreover, regulatory T cells were enumerated using CD25 and Foxp3 markers. Results: In this study, we report that the frequency of Th1 cells was increased compared to Th2 cells in infertile PCOS when considering Th1/Th2 ratio (P=0.05). Analysis of Th17/Th2 ratio showed a significant difference with a bias toward Th17 dominancy in PCOS (P=0.02). The proportion of CD4+CD25+Foxp3+ regulatory T cells was significantly lower in PCOS patients than that of healthy fertile women (P=0.02). Conclusion: In summary, Th1 and Th17 bias and reduction of Treg and Th2 cells as regulators of immune responses might be involved in the pathogenesis of PCOS. These results are suggestive of an altered immune response to inflammatory status in PCOS patients, likely causing some complications such as infertility in these patients.     

Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders

The beneficial effects of probiotics have been described in many diseases, but the mechanism by which they modulate the immune system is poorly understood. In this study, we identified a mixture of probiotics that up-regulates CD4⁺Foxp3⁺ regulatory T cells (Tregs). Administration of the probiotics mixture induced both T-cell and B-cell hyporesponsiveness and down-regulated T helper (Th) 1, Th2, and Th17 cytokines without apoptosis induction. It also induced generation of CD4⁺Foxp3⁺ Tregs from the CD4⁺CD25⁻ population and increased the suppressor activity of naturally occurring CD4⁺CD25⁺ Tregs. Conversion of T cells into Foxp3⁺ Tregs is directly mediated by regulatory dendritic cells (rDCs) that express high levels of IL-10, TGF-β, COX-2, and indoleamine 2,3-dioxygenase. Administration of probiotics had therapeutical effects in experimental inflammatory bowel disease, atopic dermatitis, and rheumatoid arthritis. The therapeutical effect of the probiotics is associated with enrichment of CD4⁺Foxp3⁺ Tregs in the inflamed regions. Collectively, the administration of probiotics that enhance the generation of rDCs and Tregs represents an applicable treatment of inflammatory immune disorders.     

Restoring homeostasis of CD4~+ T cells in hepatitis-B-virusrelated liver fibrosis

Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.     

从Th1/Th2、Treg/Th17之间的平衡研究轻、中度慢性乙型肝炎患者CD4~+T淋巴细胞的免疫失衡状态

目的从Th17及其相关细胞因子与Th1、Th2、Treg的相互关系,探讨轻、中度CHB患者CD4~+T淋巴细胞的整体免疫失衡状态。方法选择轻、中度CHB患者,与健康志愿者进行比较,观察其外周血各免疫细胞(Th17、Th1、Th2、Treg、Th1/Th2、Treg/Th17)、相关细胞因子(IL-17、IL-6、TGF-β、IFN-γ、IL-4)、主要效应分子(穿孔素、颗粒酶B)和核转录因子(孤独核受体RORγt、Foxp3等)的变化及其相互关系。结果与健康志愿者相比,CHB患者CD8~+T淋巴细胞比例更高,CD4~+/CD8~+比例显著下降,差异有统计学意义(P0.01);与健康志愿者相比,CHB患者Th1细胞比例更高,Th1/Th2显著升高,差异有统计学意义(P0.01);与健康志愿者相比,CHB患者Th17细胞比例更高,Treg/Th17比例显著下降,差异有统计学意义(P0.01);与健康志愿者相比,CHB患者穿孔素和颗粒酶B的表达更高,差异有统计学意义(P0.01);与健康志愿者相比,CHB患者FOXP3、IL17mRNA和RORγt的表达差异无统计学意义(P0.05);与健康志愿者相比,CHB患者TGF-B1、IL-6、IL-17显著增高,差异有统计学意义(P0.01);IFN-γ和IL-4的表达差异无统计学意义(P0.05)。结论轻、中度CHB患者在免疫细胞及其相关细胞因子、效应分子等各环节,尤其是Treg/Th17比例,均处于严重的免疫失衡状态。     

Foxp3⁺ regulatory T cells exert asymmetric control over murine helper responses by inducing Th2 cell apoptosis

Foxp3(+) regulatory T cells play a pivotal role in maintaining self-tolerance and immune homeostasis. In the absence of regulatory T cells, generalized immune activation and multiorgan T cell-driven pathology occurs. Although the phenomenon of immunologic control by Foxp3(+) regulatory T cells is well recognized, the comparative effect over different arms of the immune system has not been thoroughly investigated. Here, we generated a cohort of mice with a continuum of regulatory T-cell frequencies ranging from physiologic levels to complete deficiency. This titration of regulatory T-cell depletion was used to determine how different effector subsets are controlled. We found that in vivo Foxp3(+) regulatory T-cell frequency had a proportionate relationship with generalized T-cell activation and Th1 magnitude, but it had a surprising disproportionate relationship with Th2 magnitude. The asymmetric regulation was associated with efficient suppression of Th2 cells through additional regulations on the apoptosis rate in Th2 cells and not Th1 cells and could be replicated by CTLA4-Ig or anti-IL-2 Ab. These results indicate that the Th2 arm of the immune system is under tighter control by regulatory T cells than the Th1 arm, suggesting that Th2-driven diseases may be more responsive to regulatory T-cell manipulation.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.