IMMUNOREGULATORY ROLE OF GAMMA DELTA T CELLS IN TB

结核病每年在世界范围内造成的死亡人数超过任何其他疾病 传染性人类病原体 根除结核病需要 开发有效的疫苗，这反过来又取决于了解 结核病的保护性免疫机制。 免疫 回应M。结核病被认为是由T淋巴细胞介导的 能够识别分枝杆菌抗原 抗原识别是由 T细胞受体由α和β链，或γ和δ链组成 店 虽然γ δ T细胞的功能仍然未知， 越来越多的证据表明，它们参与了免疫反应， 分枝杆菌和其他病原微生物。 这个监狱 建议是研究携带γ δ T的淋巴细胞的作用 细胞受体介导的抵抗性和保护性免疫反应 结核分枝杆菌。 我们的具体目标是：1）确定 γ δ T细胞及其亚群在组织中的分布 和血液中的结核感染， 使用单和双免疫染色。 γ δ T的抗原反应性 将通过测量γ δ T细胞的百分比来评价细胞 细胞经M.结核 2)表征 γ δ T细胞识别的分枝杆菌抗原和表位 建立来自患有以下疾病的患者的γ δ T细胞系和克隆 结核感染和测试它们对分枝杆菌的反应性 抗原直接或通过T细胞蛋白质印迹技术。 表位 将通过测试γ δ T细胞克隆， 合成重叠肽。 3)功能能力评价 通过测定γ δ T细胞的淋巴因子分泌模式 和细胞毒性能力。 四、 确定编码γ的基因的多样性程度 和δ链的T细胞受体的整个频谱， 结核感染和疾病活动部位，使用PCR， 扩增相关基因片段。 有限的多样性表明， γ δ T细胞识别高度保守的抗原，如热休克 proteins. 拟议的研究将提供有关基本的信息， 关于γ δ T淋巴细胞在免疫中的功能的问题 对感染性病原体的反应。

Tuberculosis causes more deaths annually world-wide than any other infectious human pathogen. Eradication of tuberculosis will require development of an effective vaccine, which in turn hinges on understanding the mechanism of protective immunity against tuberculosis. Immune responses to M. tuberculosis are thought to be mediated by T lymphocytes that recognize mycobacterial antigens. Antigen recognition is mediated by T cell receptors composed of alpha and beta chains, or gamma and delta chains. Although the functions of gammadelta T cells remain unknown, there is growing evidence that they are involved in the immune response to mycobacteria and other pathogenic microorganisms. The gaol of this proposal is to investigate the role of lymphocytes bearing gammadelta T cell receptors in mediating resistant and protective immune responses to Mycobacterium tuberculosis. Our specific aims are: 1) Determination of the distribution of gammadelta T cells and their subpopulations in tissue and blood of patients throughout the spectrum of tuberculous infection, using single and double immunostaining. Antigen reactivity of gammadelta T cells will be evaluated by measurement of the percentage of gammadelta T cells after culture in vitro with M. tuberculosis. 2) Characterization of mycobacterial antigens and epitopes recognized by gammadelta T cells by establishing gammadelta T cell lines and clones from patients with tuberculous infection and testing their reactivity to mycobacterial antigens directly or by the T-cell Western blot technique. Epitope definition will be achieved by testing gammadelta T cell clones against synthetic overlapping peptides. 3) Evaluation of the functional capacity of gammadelta T cells by determining their pattern of lymphokine secretion and cytotoxic capacity when triggered by mycobacterial antigens. 4) Determination of the degree of diversity of the genes coding for the gamma and delta chains of the T cell receptor throughout the spectrum of tuberculous infection and at the site of disease activity, using PCR to amplify relevant gene segments. Limited diversity would suggest that gammadelta T cells recognize highly conserved antigens such as heat shock proteins. The studies proposed will provide information on fundamental questions regarding the function of gammadelta T lymphocytes in the immune response to infectious pathogens.