FUNCTION OF CD8T CELLS IN TUBERCULOSIS

CD8T 细胞在结核病中的功能

• 批准号: 6373471
• 负责人: JoAnne L. Flynn
• 金额: $ 14.82万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373471
• 关键词: MHC class II antigen; Mycobacterium tuberculosis; bactericidal immunity; cell mediated lymphocytolysis test; cellular immunity; cytokine; cytolysins; cytotoxic T lymphocyte; genetically modified animals; host organism interaction; interferon gamma; interleukin 12; laboratory mouse; pore forming protein; tissue /cell culture; tuberculosis; virulence

The bacterial pathogen, Mycobacterium tuberculosis, is responsible for 8 million new cases of tuberculosis and 2.9 million deaths per year, worldwide. The host immune responses necessary for protection against disease are not clearly defined. Cell-mediated immunity is required for protection, and recent work has confirmed a role for both CD4 and CD8 T cells in the immune response to this pathogen. Here, experiments designed to examine the exact nature of the contribution of CD8 T cells to the protective immune response are proposed. We have outlined a strategy for determining the actual function of CD8 T cells, either as cytotoxic T cells or IFN-gamma producing cells, or both, in M. tuberculosis infection. This involves testing for the presence of mycobacterial specific CD8 CTLs in various mice, establishing CTL lines, and testing these lines for protective capacity in vivo. A systematic approach to this problem is proposed, including the use of various alternative target cells and sources for CD8 T cells. As an alternative hypothesis, the role of IFN-gamma produced by CD8 T cells will be examined. Using in vitro methods and immunological complementation in gene-disrupted mice, we will determine the role of CD8 T cells in protection against tuberculosis in mice. These studies on the actual role of CD8 T cells will increase our understanding of the host immune responses necessary for protection against M. tuberculosis. Information obtained from the results of the proposed experiments will be of value in designing new immunization strategies for tuberculosis and may suggest potential pathogenic mechanisms by which mycobacteria evade the necessary immune responses, and unveil possible virulence factors for further study.

细菌病原体，结核分枝杆菌， 每年有800万新结核病例和290万人死亡， 年，全球。保护所需的宿主免疫反应 对疾病没有明确的定义。细胞介导的免疫 需要保护，最近的工作证实了 CD 4和CD 8 T细胞在对这种病原体的免疫反应中。 在这里，实验旨在研究的确切性质， CD 8 T细胞对保护性免疫应答的贡献是 提出了我们已经概述了一个战略，以确定实际的 作为细胞毒性T细胞或IFN-γ的CD 8 T细胞的功能 在M.肺结核感染。这涉及 测试在细胞中分枝杆菌特异性CD 8 CTL的存在， 不同的小鼠，建立CTL系，并测试这些系的 体内保护能力。解决这一问题的系统方法是 提出，包括使用各种替代的目标细胞， 来源于CD 8 T细胞。作为另一种假设， 将检查由CD 8 T细胞产生的IFN-γ。使用体外 方法和基因破坏小鼠的免疫互补，我们 将决定CD 8 T细胞在保护免疫系统中的作用。 小鼠肺结核这些关于CD 8 T细胞实际作用的研究 将增加我们对宿主免疫反应的理解 需要保护M。结核信息 从拟议的实验结果中获得的结果将是 制定新的结核病免疫战略的价值， 可能提示了分枝杆菌的潜在致病机制 逃避必要的免疫反应，并揭示可能的毒力 进一步研究的因素。