FUNCTION OF CD8T CELLS IN TUBERCULOSIS

细菌病原体，结核分枝杆菌，负责 每年新增800万结核病病例和290万人死亡 一年，全世界。保护所需的宿主免疫反应 对疾病的防治没有明确的定义。细胞介导的免疫是 所需的保护，最近的工作证实了 CD4和CD8T细胞都参与了对这种病原体的免疫反应。 在这里，设计的实验是为了检查 CD8 T细胞在保护性免疫反应中的作用 建议。我们已经概述了一种确定实际情况的策略 CD8 T细胞作为细胞毒T细胞或干扰素-γ的功能 在结核分枝杆菌感染中产生细胞或两者兼而有之。这涉及到 分枝杆菌特异性CD8 CTL的检测 各种小鼠，建立CTL系，并测试这些系 体内保护能力。解决这个问题的系统方法是 提议，包括使用各种替代目标单元和 CD8 T细胞的来源。作为另一种假设， 将检测CD8T细胞产生的干扰素-γ。在体外使用 方法和在基因突变小鼠中的免疫互补 将确定CD8 T细胞在预防疾病中的作用 小鼠的肺结核。CD8 T细胞实际作用的研究 将增加我们对宿主免疫反应的了解 对于预防结核分枝杆菌来说是必要的。信息 从建议的实验结果中获得的结果将是 设计新的结核病免疫策略的价值和 可能暗示了分枝杆菌可能的致病机制 逃避必要的免疫反应，揭示可能的毒力 有待进一步研究的因素。

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.