DIFFERENTIAL ACTIVATION REQUIREMENTS OF CD4+ T CELLS

说明(改编自申请人的摘要)：规则 免疫反应严重依赖于T细胞的发育 产生特定细胞因子谱而不产生其他细胞因子谱的子集，例如Th1 对抗Th2细胞因子，对抗原刺激的反应。此外， 感染各种病原体的结局由以下因素决定 抗原特异的CD4+T细胞产生的细胞因子，以及不适当的 Th2细胞因子的产生可导致感染或 在过敏性疾病中，虽然不适当地产生Th1细胞因子可以 导致自身免疫病理。这个项目的长期目标是 为了阐明控制发育、激活和 抗原中细胞因子谱受限的CD4+T细胞的功能 具体的回应。在前一个项目期间，它被演示了 抗原提呈细胞(APC)类型、细胞因子如IL-12和 APC产生的IL-10及其在APC水平表达的遗传因素 在调控细胞因子谱中发挥重要作用 CD4+T细胞。本应用程序的目标是进一步阐明这些 关键元素允许APC引导CD4+细胞因子谱的发展 T细胞。具体地说，这些研究将：1.检查巨噬细胞如何 不同品系小鼠对IL-4和干扰素-γ的不同调节作用 在抗原特异性免疫反应过程中；2.确定差异如何 不同品系小鼠的B细胞控制IL-4和 在CD4+T细胞中产生干扰素-γ；3.通过 哪些B细胞可诱导CD4+T细胞合成IL-4。从以下方面获得的见解 关于规范的精确机制的建议研究(S) 细胞因子合成应突出潜在的治疗方法 以优化发展合适的T细胞亚群。

DESCRIPTION (Adapted from the Applicant's abstract): The regulation of immune responses is critically dependent on the development of T-cell subsets which produce particular cytokine profiles and not others, e.g., Th1 versus Th2 cytokines, in response to antigenic stimuli. In addition, the outcome of infection with a variety of pathogens is determined by the cytokines produced by antigen specific CD4+ T-cells, and inappropriate production of Th2 cytokines can result in the dissemination of infection or in allergic disease, while inappropriate production of Th1 cytokines can result in autoimmune pathology. The long term objective of this project is to elucidate the mechanisms that govern the development, activation and function of CD4+ T-cells with restricted cytokine profiles in antigen specific responses. In the previous project period, it was demonstrated that the antigen presenting cell (APC) type, cytokines such as IL-12 and IL-10 produced by APC, and genetic factors expressed at the level of the APC play a major role in governing the cytokine profile which develops in the CD4+ T-cell. The goal of this application is to further elucidate how these key elements allow APC to direct the developing cytokine profile in CD4+ T-cells. Specifically, these studies will: 1. Examine how macrophages from distinct strains of mice differentially regulate IL-4 and IFN-gamma during antigen specific immune responses; 2. Determine how differences in B-cells from distinct strains of mice control the quantity of IL-4 and IFN-gamma produced in CD4+ T-cells; 3. Examine the molecular mechanisms by which B-cells induce IL-4 synthesis in CD4+ T-cells. Insights gained from the proposed studies regarding the precise mechanism(s) that regulate cytokine synthesis should highlight potential therapeutic approaches likely to optimize the development of the appropriate T-cell subset.