MECHANISMS OF T CELL DYSFUNCTION IN HCV PERSISTENCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在此期间取得的进展主要集中在了解慢性丙型肝炎患者的肝脏免疫反应和表征这些患者的肝内CD8+T细胞的功能缺陷。 对慢性丙型肝炎患者的研究发现，肝脏浸润性CD8+T细胞高度活化，但它们在增殖能力、细胞因子产生和效应分子产生方面存在严重缺陷，这与PD-1高表达和IL-2信号低有关。这些细胞也容易受到细胞因子撤除介导的细胞凋亡的影响。除了这项工作外，我们还招募了自然缓解的丙型肝炎病毒感染患者，以评估这些患者的丙型肝炎病毒特异性CD8+T细胞的表型、PD-1表达和功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The thrust of progress during this period centered on understanding liver immune responses in patients with chronic HCV infection and characterizing the functional deficits of intrahepatic CD8+ T cells from these patients. Studying patients with chronic HCV infection, we find that liver infiltrating CD8+ T cells are highly activated, but they display profound deficits in proliferative capacity, cytokine production, and effector molecule production that was linked to high PD-1 expression and low IL-2 signaling. These cells also are susceptible to a cytokine withdrawal mediated apoptosis. In addition to this work, we have enrolled patients with spontaneous resolution of HCV infection in order to evaluate the phenotype, PD-1 expression and functionality of HCV specific CD8+ T cells from these patients.