T cell subsets in murine mycoplasma respiratory disease

长期目标是确定免疫和炎症反应对 支原体呼吸道疾病的进展和耐药性，并将这些信息应用于支原体呼吸道疾病的开发 针对支原体疾病的有效免疫疗法。支原体是#年肺部疾病的主要原因。 人类。针对支原体的免疫反应可以是保护性的，也可以是促进炎症性疾病的。这些 研究利用了一种由肺炎支原体引起的小鼠呼吸道支原体疾病模型。这是一个 自然宿主中的病原体，引起类似于人类支原体肺炎的疾病。在过去的奖项中 在此期间，T细胞反应被证明是支原体呼吸系统疾病发病的关键决定因素。 这一建议涉及以下几个方面：1)支原体病期间Th细胞的产生是如何反应的 发病机制还是免疫后影响疾病进展？Th2反应被假设为 支原体肺部疾病的免疫病理学，而Thl反应有助于耐药。2)角色是什么 抗支原体CD8+T细胞在抑制疾病中的作用？CD8+T细胞对支原体的反应是 假设调节Th细胞反应参与炎症损伤的发病机制；3)Do CD4+CD25+Treg细胞对影响支原体疾病进展的T细胞反应有影响吗？它是 假设CD4+CD25+Treg细胞调节适应性T细胞对支原体感染的反应，这是 可能有助于持续感染，同时抑制免疫介导的炎症。4)什么是 T细胞群对小鼠肺炎支原体病的影响？开始审视T的作用 由人类病原体肺炎支原体引起的细胞疾病，我们将利用一个小鼠模型来研究这一点 感染。我们推测，在疾病中发现的免疫机制是由自然病原体M。 肺脏，将被类似地激活，并在小鼠的肺炎支原体疾病中发挥类似的作用。实验性的 设计如下：1)来自正常小鼠和细胞因子基因敲除小鼠的Th细胞将被过继转移并影响 关于支原体疾病的检查。同样将使用支原体特异性Th亚群细胞系；2)体外 用Th细胞培养和过继转移将检测CD8+T细胞对T细胞的影响 支原体特异性Th细胞激活；3)CD25+细胞在小鼠体内将被特异性抗体耗尽，而 将在IL-10基因敲除小鼠和活体内检测感染的持久性和疾病的发病机制 将检查使用抗体治疗的情况。此外，CD4+CD25+T细胞和Th细胞在裸鼠体内的重建 细胞将被用来检查对支原体疾病的影响；4)研究将与 确定T细胞在肺炎支原体病小鼠模型中的作用。

The long-term objective is to determine the immunologic and inflammatory responses that have an impact on the progression and resistance to mycoplasma respiratory disease, and apply this information to development of effective immunotherapies against mycoplasma diseases. Mycoplasmas are a major cause of lung disease in humans. Immune responses against mycoplasma can either be protective or promote inflammatory disease. These studies take advantage, of a murine model of mycoplasma respiratory disease due to M. pulmonis. This is a pathogen in its natural host and causes disease similar to human mycoplasma pneumonia. In the past award period, T cell responses were shown to be critical determinants in mycoplasma respiratory disease pathogenesis. This proposal addresses the following: 1) How does generation of Th cell responses during mycoplasma disease pathogenesis or after immunization influence disease progression? Th2 responses are hypothesized to be immunopathologic in mycoplasma lung disease while Thl responses contribute to resistance. 2) What is the role of anti-mycoplasma CD8+ T cells in dampening disease? CD8+ T cell responses against mycoplasma are hypothesized to regulate Th cell responses involved in the pathogenesis of inflammatory lesions; 3) Do CD4+CD25+ Treg cells have an effect on T cell responses that influence progression of mycoplasma disease? It is hypothesize that CD4+CD25+ Treg cells modulates adaptive T cell responses against mycoplasma infection, which may contribute to persistence of infection while dampening immune-mediated inflammation. 4) What is the influence of T cell populations on murine Mycoplasma pneumoniae disease? To begin to examine the role of T cells in disease due to the human pathogen, M. pneumoniae, we will take advantage of a murine model of this infection. We hypothesize that the immune mechanisms found in disease due to the natural pathogen, M. pulmonis, will be similarly activated and play similar roles in M. pneumoniae disease in mice. The experimental designs are: 1) Th cells from normal and cytokine knockout mice will be adoptively transferred and their impact on mycoplasma disease examined. Mycoplasma-specific Th subset cell lines will similarly be used; 2) In vitro culture with Th cells and adoptive transfer of will be used examine the impact of CD8+ T cells on mycoplasma-specific Th cell activation; 3) CD25+ cells will be depleted in mice using specific antibody, and the persistence of infection and pathogenesis of disease will be examined in IL-10 knockout mice, and in vivo treatment with antibodies will examined. In addition, reconstituion of nude mice with CD4+CD25+ T cells and Th cells will be used to examine the effect on mycoplasma disease; and 4) Studies will be done in parallel to determine the role of T cells in a murine model of M. pneumoniae disease.