The role of regulatory T cells in M. tuberculosis infection

越来越多的证据表明，TGFAP在预防自身免疫中起着关键作用， 抑制移植物排斥，抑制对肿瘤的免疫应答， 微生物病原体然而，关于TdR在以下方面的作用的信息有限： 感染M.结核病是一种导致巨大发病率的病原体， 全球范围内的死亡率。最近，我们发现，在健康的结核菌素反应器中， 增强单核细胞产生前列腺素E2（PGE2），PGE2有利于 扩展的Tibet。此外，NK细胞抑制Treg响应于M. 通过直接溶解结核杆菌来治疗结核病。这项建议将使这些机制具有以下特点： 哪些巨噬细胞和NK细胞影响健康结核菌素中TbR的扩增 反应堆通过以下目标。1)确定细胞机制， M.结核病感染的单核细胞扩增T细胞。我们将识别出可溶性T细胞 因子和介导T细胞的因子：单核细胞细胞与细胞接触， PGE_2的产生和T细胞的扩增是对M.肺结核感染。的 还将鉴定有利于Treg扩增的单核细胞亚群。2)确定 NK细胞抑制T细胞扩增的机制，重点是 NK细胞裂解TcB的机制。这些研究将提供一个改进的 了解调节调节性调节性T细胞扩增的机制， 细胞内细菌感染。获得的信息将帮助我们设计更多 有效的抗结核疫苗，并为开发 基于抑制Treg发育的免疫抑制策略。

Mounting evidence indicates that Tregs play a critical role in preventing autoimmunity, inhibiting transplant graft rejection, suppressing immune response to tumors and to microbial pathogens. However limited information is available about the role of Tregs in infection due to M. tuberculosis, a pathogen that causes tremendous morbidity and mortality world-wide. Recently, we found that, in healthy tuberculin reactors, T-cells enhance production of prostaglandin E2 (PGE2) by monocytes, and PGE2 favors expansion of Tregs. In addition, NK cells inhibit Treg expansion in response to M. tuberculosis by direct lysis of Tregs. This proposal will characterize the mechanisms by which macrophages and NK cells affect expansion of Tregs in healthy tuberculin reactors through the following aims. 1) Determine the cellular mechanisms by which M. tuberculosis-infected monocytes expand Tregs. We will identify the soluble T cell factors and the factors mediating T-cell:monocyte cell-to-cell contact that increase PGE2 production and expand Tregs in response to M. tuberculosis infection. The monocyte subpopulation that favors Treg expansion will also be identified. 2) Determine the mechanisms by which NK cells inhibit expansion of Tregs, focusing on mechanisms by which NK cells lyse Tregs. These studies will provide an improved understanding of the mechanisms that mediate Treg expansion in the response to intracellular bacterial infection. The information gained will help us to design more effective antituberculosis vaccines, and to lay the groundwork for developing immunotherapeutic strategies based on inhibiting Treg development.