The role of regulatory T cells in M. tuberculosis infection

调节性 T 细胞在结核分枝杆菌感染中的作用

• 批准号: 7534987
• 负责人: Ramakrishna Vankayalapati
• 金额: $ 17.19万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534987
• 关键词: Affect; Animal Model; Antitubercular Agents; Attention; Autoimmunity; Bacteria; Bacterial Infections; CD4 Positive T Lymphocytes; Cells; Cessation of life; Cytolysis; Development; Dinoprostone; Graft Rejection; Human; IL2RA gene; Immune response; Immunity; Immunotherapeutic agent; Individual; Infection; Interferons; Interleukin-10; Mediating; Morbidity - disease rate; Mycobacterium tuberculosis; Natural Killer Cells; Organ Transplantation; Persons; Play; Population; Production; Protozoa; Resistance to infection; Role; T-Lymphocyte; TCF Transcription Factor; TGFB1 gene; Transplantation; Tuberculin; Tuberculosis; Vaccines; Virus; base; design; improved; macrophage; microbial; monocyte; mortality; pathogen; prevent; response; tool; tumor

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.

越来越多的证据表明，Tregs在防止自身免疫性方面起着关键作用， 抑制移植移植的排斥反应，抑制对肿瘤的免疫反应和对 微生物病原体。但是，有关Tregs在中的作用的信息有限 因结核分枝杆菌引起的感染，这种病原体会引起巨大的发病率和 全球死亡率。最近，我们发现，在健康的结核蛋白反应堆中，T细胞 通过单核细胞增强前列腺素E2（PGE2）的产生，PGE2偏爱 tregs的扩展。另外，NK细胞抑制了Treg的响应。 Tregs直接溶解结核病。该建议将通过 哪些巨噬细胞和NK细胞会影响健康结核蛋白中Treg的扩张 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展了Tregs。我们将确定可溶的T单元 因素和介导T细胞的因素：单核细胞到细胞接触，增加 PGE2生产并扩大了Tregs，以响应结核分枝杆菌感染。这 也将确定有利于Treg扩展的单核细胞亚群。 2）确定 NK细胞抑制Treg的扩张的机制，重点是 NK细胞裂解Tregs的机制。这些研究将提供改进的 理解介导Treg扩展的机制 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，并为开发奠定基础 基于抑制Treg开发的免疫治疗策略。