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+4T细胞反应

目的探讨CD+4 CD+25调节性T细胞(CD+4 CD+25Treg细胞)在持续性HCV感染患者CD+4 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CD+4 CD+25Treg细胞的数量以及细胞内因子的合成;与正常人或患者CD+4 CD-25 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 CD+4 CD+25Treg细胞约占慢性丙型肝炎患者外周血中CD+4 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;CD+4 CD+25Treg细胞显著抑制CD+4 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CD+4 CD+25Treg细胞表达增加,抑制活性增强,特异性抑制Th1反应.

CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection

OBJECTIVE: To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+) CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent infection of hepatitis C viruses. METHODS: Flow cytometry was used to determine the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of Foxp3 were measured by RT-PCR. RESULTS: CD(4)(+) CD(25)(+) Treg cells comprised (13.5 +/- 1.8)% of peripheral CD(4)(+) 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). CD(4)(+) CD(25)(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells dramatically suppressed the proliferation of CD(4)(+) T cells and the production of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) 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 beta independent. CONCLUSION: Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+) Treg cells, which could function in a highly regulatory capacity to suppress Th1 response.