CD_4^+CD_(25)^+调节性T细胞抑制持续性丙型肝炎病毒感染患者CD_4^+T细胞反应

CD_4^+ CD_(25)^+ regulatory T cells suppress CD_4^+ T cell responses in patients with persistent hepatitis C virus infection

目的探讨CD4+CD2+5调节性T细胞(CD4+CD2+5TREG细胞)在持续性HCV感染患者CD4+T细胞下调中的意义。方法流式细胞术检测慢性丙型肝炎患者外周血中CD4+CD2+5TREG细胞的数量以及细胞内因子的合成;与正常人或患者CD4+CD25-T细胞共同培养,检测其抑制功能;RT-PCR检测FOXP3的MRNA表达。结果CD4+CD2+5TREG细胞约占慢性丙型肝炎患者外周血中CD4+T细胞的(13.5±1.8)%,高于正常对照(5.3±0.8)%(P=0.004);主要合成IL-10,高表达FOXP3;CD4+CD25+TREG细胞显著抑制CD4+T细胞的增殖,以及合成IFNΓ,并且抑制活性较正常人增高(P=0.034),这种作用不依赖IL-10和转化生长因子Β。结论持续性HCV感染患者CD4+CD2+5TREG细胞表达增加,抑制活性增强,特异性抑制TH1反应。

Objective To study the role of CD4^＋CD25^＋ regulatory T cells （CD4^＋CD25^＋ Treg cells） in CD4^＋ T cell responses in patients with persistent infection of hepatitis C viruses. Methods Flow cytometry was used to determine the number of CD4^＋CD25^＋ Treg cells and intracellular cytokine production by CD4^＋CD25^＋ Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD4^＋CD25^＋ Treg cells were co-cultured with CCD4^＋CD25^＋ T cells from patients or controls ; the expressions of Foxp3 were measured by RT-PCR. Results CD4^＋CD25^＋ Treg cells comprised （ 13.5 ± 1.8） % of peripheral CD4^＋ T cells in the blood of persistent hepatitis C virus infected patients, which was significantly higher than that of healthy controls （5.3 ±0. 8）% （P =0. 004）. CD4^＋CD25^＋Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD4^＋CD25^＋Treg ceils dramatically suppressed the proliferation of CD4^＋ T ceils and the production of IFNγ; the suppressive activity of CD4^＋CD25^＋ Treg cells in patients with persistent HCV-infection was higher than that in healthy controls （ P = 0. 034）. These effects were dose-dependent but IL-10 and transforming growth factor β independent. Conclusion Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD4^＋CD25^＋Treg cells, which could function in a highly regulatory capacity to suppress Thl response.