CD8+ T CELLS AND MYCOPLASMA TUBERCULOSIS

这份科学家导师奖(KO-8)的申请书寻求为David H.Canaday，M.D.提供为期5年的结核分枝杆菌感染细胞免疫学和细胞生物学研究培训资金。研究培训将由W.Henry Boom，M.D.和Clifford V.Harding，M.D.-Ph.D.在凯斯西储大学传染病学部和医学系提供。将为Canaday博士的培训提供重点的研究提案概述如下。结核分枝杆菌通过吸入雾化分枝杆菌在人与人之间传播。大多数健康的人不会患上临床结核病。相反，细胞免疫反应被激活，并能够成功地控制活跃的感染。T细胞在调节细胞免疫反应中起着至关重要的作用。T细胞亚群(CD4+、CD8+、Gammadelta+)由分枝杆菌抗原激活，但对不同T细胞亚群在结核分枝杆菌保护性免疫应答中的作用和功能知之甚少。虽然CD4+T细胞一直是许多研究的重点，但CD8+T细胞是结核分枝杆菌保护性免疫反应中重要的辅助T细胞亚群。最近我们和其他人的研究表明，人CD8+T细胞作为结核分枝杆菌感染巨噬细胞的CTL，产生干扰素-γ，并被分枝杆菌抗原激活。目前研究的主要目标是确定刺激人CD8+T细胞的分枝杆菌蛋白谱系，检测巨噬细胞在MHC I类分子上呈递结核分枝杆菌抗原的抗原处理机制，以及确定活动性结核病患者CD8+T细胞的功能。目的：1.确定人α-βTCR+CD8+T细胞识别的分枝杆菌蛋白和多肽。目的2.探讨结核分枝杆菌感染的巨噬细胞通过MHC-I类分子加工和呈递分枝杆菌蛋白的机制(S)。目的3.研究活动性结核分枝杆菌感染患者CD8+T细胞对特定蛋白和多肽的功能反应。

This application for a mentored scientist award (KO-8) seeks 5 years of funding for research training in the cellular immunology and cell biology of M. tuberculosis infection for David H. Canaday, M.D. Research training will be provided by W. Henry Boom, M.D. and Clifford V. Harding, M.D.-Ph.D. in the Division of Infectious Diseases and the Department of Medicine at Case Western Reserve University. The research proposal which will provide the focus for Dr. Canaday's training is outlined below. M. tuberculosis is spread from person to person by inhalation of aerosolized mycobacteria. Most healthy people do not develop clinical tuberculosis. Instead, cellular immune responses become activated and are able to successfully control the active infection. T cells play a crucial role in regulating the cellular immune response. T cell subsets(CD4+, CD8+, gammadelta+), are activated by mycobacterial antigens, yet little is known about the roles and function of the different T cell subsets in the protective immune response to M. tuberculosis. While CD4+ T cells have been the focus of many studies, CD8+ T cells are an important accessory T cell subset in the protective immune response to M. tuberculosis. Recent studies by us and others have demonstrated that human CD8+ T cells serve as CTL for M. tuberculosis infected macrophages, produce IFN-gamma and are activated by mycobacterial antigens. The broad goal of the current studies is to determine the repertoire of mycobacterial proteins which stimulate human CD8+ T cells, to examine the antigen processing mechanism the macrophages use to present M. tuberculosis antigens on MHC class I molecules, and to determine the function of CD8+ T cells in patients with active tuberculosis. The Aims are: Aim 1. To determine the mycobacterial proteins and peptides recognized by human alphabeta TCR+ CD8+ T cells. Aim 2. To determine the mechanism(s) used by M. tuberculosis infected macrophages to process and present mycobacterial proteins by MHC class I molecules. Aim 3. To characterize the functional CD8+ T cell responses to specific proteins and peptides from in patients with active M. tuberculosis infection.