CD8+ T CELLS AND MYCOPLASMA TUBERCULOSIS

本次申请的指导科学家奖（KO-8）为David H. Canaday医学博士寻求为期5年的研究培训资金，用于研究结核杆菌感染的细胞免疫学和细胞生物学。研究培训将由W. Henry Boom医学博士和Clifford V. Harding医学博士提供。在凯斯西储大学传染病系和医学系任职。研究计划将为卡纳迪博士的培训提供重点，概述如下。结核分枝杆菌通过吸入雾化的分枝杆菌在人与人之间传播。大多数健康人不会发展为临床结核病。相反，细胞免疫反应被激活，并能够成功地控制活动性感染。T细胞在调节细胞免疫应答中起着至关重要的作用。T细胞亚群（CD4+, CD8+, γ - δ +）可被分枝杆菌抗原激活，但人们对不同T细胞亚群在对结核分枝杆菌的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焦点，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。我们和其他人最近的研究表明，人CD8+ T细胞作为结核分枝杆菌感染巨噬细胞的CTL，产生ifn - γ并被分枝杆菌抗原激活。当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库，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加工机制，以及确定CD8+ T细胞在活动性结核病患者中的功能。目标是：目标1；测定人TCR+ CD8+ T细胞识别的分枝杆菌蛋白和多肽。目标2。确定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。目标3。目的探讨活动性结核分枝杆菌感染患者CD8+ T细胞对特异性蛋白和肽的功能反应。

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.