Functional suppression by FoxP3+CD4+CD25high regulatory T cells during acute hepatitis C virus infection
Functional suppression by FoxP3+CD4+CD25high regulatory T cells during acute hepatitis C virus infection
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DOI：
10.1086/523651
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发表时间：
2008-01-01
影响因子：
6.4
通讯作者：
Rosen, Hugo R.
中科院分区：
文献类型：
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作者：
Smyk-Pearson, Susan;Golden-Mason, Lucy;Rosen, Hugo R.
背景资料。丙型肝炎病毒感染的特征是病毒效应性T细胞反应受损和病毒持续存在的高倾向。先前的研究表明，与感染缓解的人和健康人相比，慢性丙型肝炎病毒感染与调节性T(T-reg)细胞的频率增加有关。然而，在先前的分析中，所有患者都有遥远的过去接触史，因此无法确定Treg细胞在感染的最早阶段是否在建立持久性方面发挥了因果作用，或者它们是否是因为病毒持久性而扩大。我们首次纵向分析了27例急性丙型肝炎患者的T-reg细胞。我们使用了多参数方法，包括细胞表面和细胞内抗原的荧光激活细胞分选分析，与高纯度的CD4(+)CD25(高)调节细胞和CD4(+)CD25(-)应答细胞共培养实验，以及分泌细胞因子的多重分析。在急性丙型肝炎患者中，Forkhead转录因子3(FoxP3)的表达和Treg细胞抑制高于健康对照组，但在随后出现持续性或自发消退的患者中，在最初的时间点没有差异；然而，6个月后，疾病的缓解与相对功能抑制的丧失有关。总而言之，这些数据表明，急性丙型肝炎病毒感染患者的T-reg细胞功能表现出时间上的变化。随着时间的推移，重复的病毒抗原刺激可能会改变T-reg细胞的功能。
Background. Infection with hepatitis C virus (HCV) is characterized by impairment of viral effector T cell responses and a high propensity for viral persistence. Previous studies have demonstrated that chronic HCV infection is associated with an increased frequency of regulatory T (T-reg) cells, compared with that in persons whose infection resolved and in healthy persons. However, all patients in prior analyses had exposures in the distant past, precluding the ability to determine whether Treg cells play a causal role in establishing persistence during the earliest stages of infection or whether they are expanded because of viral persistence.Methods. For the first time, we longitudinally analyzed T-reg cells in patients with acute HCV infection (n = 27). We used a multiparameter approach, including fluorescence-activated cell sorting analysis of cell-surface and intracellular antigens, coculture experiments with highly purified CD4(+) CD25(high) regulatory and CD4(+)CD25(-) responder cell populations, and multiplex analysis of secreted cytokines.Results. Forkhead transcription factor 3 (FoxP3) expression and Treg cell suppression were greater in patients with acute HCV infection than in healthy control subjects but were not different at the first time point among patients who subsequently developed persistence or resolved HCV infection spontaneously; however, 6 months later, the resolution of disease was associated with a relative loss of functional suppression.Conclusions. Collectively, these data indicate that patients with acute HCV infection who develop chronicity versus spontaneous resolution exhibit temporal changes in T-reg cell function. It is possible that repetitive viral antigenic stimulation alters the function of T-reg cells over time.