CELLULAR IMMUNE RESPONSES IN SIV-INFECTED SOOTY MANGABEYS

感染 SIV 的乌白眉猴的细胞免疫反应

• 批准号: 7715437
• 负责人: Amitinder Kaur
• 金额: $ 12.98万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715437
• 关键词: Accounting; Avidity; Biological Assay; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Cercocebus; Cercocebus atys; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Data; Funding; Gagging; Grant; Human; Immune Tolerance; Immune response; Infection; Institution; Interferon Type II; Lymphocyte Depletion; Macaca mulatta; Maintenance; Mediating; Mus; Peripheral; Peripheral Blood Mononuclear Cell; Range; Recovery; Research; Research Personnel; Resources; Role; SIV; Source; Spottings; Staining method; Stains; United States National Institutes of Health; Viremia; cytokine; env Gene Products; in vivo; response

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 role of SIV-specific cellular immune responses in maintaining nonpathogenic SIV infection in sooty mangabeys is being investigated using Elispot and intracellular cytokine staining assays as well as by in vivo CD8+ T lymphocyte depletion studies. In vivo CD8 depletion using the mouse-human chimeric anti-CD8 mAB cM-T807 resulted in a two-log or greater increase in SIV viremia in 5/6 mangabeys. Return of SIV viremia levels to baseline values was coincident with recovery of peripheral CD8+ T lymphocytes. These data suggest that CD8+ T lymphocytes do inhibit SIV replication in vivo in SIV-infected sooty mangabeys. In a cross-sectional analysis, positive SIV-specific interferon-gamma Elispot responses ranging between 510-5244 spot forming cells per million PBMC were observed in 25/25 SIV-infected mangabeys and were comparable to that observed in four rhesus macaques infected for more than one year with SIVmac251. In the majority of sooty mangabeys, the interferon-gamma responses to SIV Gag and/or Env proteins accounted for at least two-thirds of the total SIV-specific response. In 9 mangabeys examined, the interferon-gamma responses to Gag and Env were predominantly mediated by high avidity CD8+ T lymphocytes. Naturally SIV-infected sooty mangabeys mount a substantial SIV-specific cellular immune response, suggesting that immune tolerance is neither a feature nor a requirement for maintenance of nonpathogenic infection in this natural host of SIV infection.

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。 SIV特异性细胞免疫反应在使用ELISPOT和细胞内细胞因子染色测定法以及体内CD8+ T淋巴细胞衰减研究中研究了SIV特异性细胞免疫反应在烟草芒果中维持非对照SIV感染的作用。 使用小鼠人类嵌合抗CD8 mAb CM-T807的体内CD8耗竭导致5/6 Mangabeys的SIV病毒血症增加了两位或更高的增加。 SIV病毒血症水平回到基线值与外围CD8+ T淋巴细胞的恢复是一致的。 这些数据表明，CD8+ T淋巴细胞在SIV感染的烟草芒果中会抑制体内SIV复制。 在横截面分析中，在25/25 SIV infected Mangabeys中观察到510-5244斑点形成510-5244的斑点形成细胞在510-5244斑点形成细胞之间的阳性阳性，与在SIV siv Macaques感染了一年以来，在四个鼠尾草中观察到的25/25斑点是510-5244个斑点形成细胞。 在大多数烟草芒果中，对SIV堵嘴和/或ENV蛋白的干扰素伽马反应至少占SIV特异性响应的三分之二。在检查的9个芒果中，对GAG和ENV的干扰素 - 伽马反应主要由高自发性CD8+ T淋巴细胞介导。 自然感染了SIV的烟囱芒果载有大量的SIV特异性细胞免疫反应，这表明免疫耐受性既不是在这种天然SIV感染宿主中维持非致病性感染的特征，也不是维持非致病性感染的需求。