MECHANISMS OF T CELL DYSFUNCTION IN HCV PERSISTENCE

HCV 持续存在中 T 细胞功能障碍的机制

• 批准号: 8172459
• 负责人: HENRY Thomas RADZIEWICZ
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172459
• 关键词: Apoptosis; CD8B1 gene; Cells; Chronic Hepatitis C; Computer Retrieval of Information on Scientific Projects Database; Enrollment; Functional disorder; Funding; Grant; Hepatitis C; Hepatitis C virus; Immune response; Institution; Interleukin-2; Link; Liver; Mediating; Patients; Phenotype; Production; Research; Research Personnel; Resolution; Resources; Signal Transduction; Source; T-Lymphocyte; United States National Institutes of Health; Withdrawal; Work; cytokine; intrahepatic

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在此期间，进步的推力是了解慢性HCV感染患者的肝免疫反应，并表征了这些患者肝内CD8+ T细胞的功能缺陷。 研究患有慢性HCV感染的患者，我们发现肝脏浸润的CD8+ T细胞被高度激活，但它们在增殖能力，细胞因子产生和效应分子的产生中表现出严重的缺陷，与高PD-1表达和低IL-2信号有关。 这些细胞还易受细胞因子戒断介导的细胞凋亡的影响。除这项工作外，我们还招募了HCV感染自发分辨率的患者，以评估来自这些患者的HCV特异性CD8+ T细胞的表型，PD-1表达和功能。