T cell subsets in murine mycoplasma respiratory disease

长期的目标是确定免疫学和炎症反应，这些反应对 支原体呼吸道疾病的进展和耐药性，并将此信息应用于开发 有效的免疫治疗支原体疾病。支原体是肺部疾病的主要原因， 人类针对支原体的免疫应答可以是保护性的或促进炎性疾病。这些 研究利用了由支原体引起的支原体呼吸道疾病的小鼠模型。肺动脉这是一 病原体在其自然宿主中，并引起类似于人类支原体肺炎的疾病。在过去的奖项 T细胞应答是支原体呼吸道疾病发病机制的关键决定因素。 该建议解决了以下问题：1）支原体疾病期间Th细胞应答的产生如何影响 发病机制或免疫后影响疾病进展？Th 2应答被假设为 在支原体肺病免疫病理学中，Thl应答有助于抗性。2)有什么作用 抗支原体CD 8 + T细胞在疾病中的作用CD 8 + T细胞对支原体的应答是 假设调节Th细胞反应参与炎性病变的发病机制; 3） CD 4 + CD 25 + Treg细胞对影响支原体疾病进展的T细胞应答有影响？是 假设CD 4 + CD 25 + Treg细胞调节针对支原体感染的适应性T细胞应答， 可能有助于感染的持续，同时抑制免疫介导的炎症。4)是什么 T细胞群对小鼠肺炎支原体病影响？开始检查T的作用 细胞的疾病，由于人类病原体，M。肺炎，我们将利用这种小鼠模型， 感染我们假设，在疾病中发现的免疫机制是由于自然病原体M。 肺M.小鼠肺炎性疾病。实验 设计是：1）来自正常和细胞因子敲除小鼠的Th细胞将被过继转移，并且它们的影响 对支原体病进行检查。类似地使用支原体特异性Th亚群细胞系; 2）体外 将使用Th细胞培养和过继转移来检查CD 8 + T细胞对 支原体特异性Th细胞活化; 3）使用特异性抗体将小鼠中的CD 25+细胞耗尽，并且 将在IL-10敲除小鼠中检查感染的持续性和疾病的发病机制，并在体内 将检查抗体治疗。此外，用CD 4 + CD 25 + T细胞和Th细胞重建裸鼠， 细胞将用于检查对支原体疾病的影响;和4）研究将与 确定T细胞在小鼠M.肺炎疾病。

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.