DIFFERENTIAL ACTIVATION REQUIREMENTS OF CD4+ T CELLS

该项目的长期目标是进一步了解 调控CD 4 + T细胞的发育、活化和功能的机制 在抗原特异性应答中具有限制性细胞因子谱的细胞。 该项目的目标是： 1.确定细胞因子谱发展的精确机制， 钥孔血蓝蛋白（KLH）特异性记忆T细胞，以及如何类型 抗原提呈细胞（APC）及其活化状态，抗原 浓度，APC共刺激分子影响这种发展。 2.分析细胞因子的合成是如何被差异调节的， 不同品系的老鼠 3.比较B细胞在引导淋巴因子发育中的作用 在致敏与未致敏的CD 4 + T细胞中的分布。 为了实现这些目标，我们已经建立了几种抗原特异性 模型来跟踪限制性淋巴因子谱的发展。 我们 已经产生了大量的初步数据， 在KLH致敏的CD 4 + T细胞中IL-4的合成受到 KLH在体外的浓度，并优先增强抗原 由致敏的B细胞呈递。 此外，我们还有几条生产线， 有证据表明，淋巴因子合成的调节是 在不同品系的小鼠中不同，这是由于 抗原呈递细胞 最后，我们建立了准确和 对细胞因子IL-2、IL-3和IL-4、IL-5、IL-6的敏感测定， IL-10、IFN-γ。 在尽可能多的反应，以不同类型的病原体-需要不同的 功能的T细胞，T细胞亚群的发展与限制 细胞因子谱在调节细胞因子中具有根本的重要性。 免疫反应 了解调节细胞生长的精确机制， CD 4 + T细胞亚群的发展对于理解和 治疗疾病，如过敏，自身免疫性疾病， 感染或癌症，以及疫苗开发，其中 具有不适当的细胞因子谱的CD 4 + T细胞的发展可能是 对宿主有害。

The long term goals of this project are to gain further insight into the mechanisms that govern the development, activation and function of CD4+ T cells with restricted cytokine profiles in antigen specific responses. The objectives of this project are to: 1. Determine the precise mechanisms by which cytokine profiles develop in keyhole limpet hemocyanin (KLH)-specific memory T cells, and how the type of antigen presenting cell (APC) and its activation state, antigen concentration, and APC costimulator molecules influence this development. 2. Analyze how cytokine synthesis is differentially regulated in different strains of mice. 3. Compare the role of B cells in directing the development of lymphokine profiles in primed versus unprimed CD4+ T cells. To accomplish these aims we have established several antigen specific models to follow the development of restricted lymphokine profiles. We have generated a substantial amount of preliminary data demonstrating that IL-4 synthesis in KLH primed CD4+ T cells is greatly affected by the concentrations of KLH in vitro, and is preferentially enhanced by antigen presentation by primed B cells. In addition, we have several lines of evidence that indicate that regulation of lymphokine synthesis is distinct in different strains of mice, due to differences at the level of the antigen presentation cell. Finally, we have established accurate and sensitive assays for the cytokines IL-2, IL-3 and IL-4, IL-5, IL-6, IL-10, IFN-gamma. In as much as responses to different types of pathogens-require distinct functions of T cells, the development of T cell subsets with restricted cytokine profiles is of fundamental importance in regulation of the immune response. Knowledge of the precise mechanisms that regulate the development of CD4+ T cells subsets is critical in understanding and treating diseases such as allergy, autoimmune disease, susceptibility to infection, or cancer, and in vaccine development, in which the development of CD4+ T cells with inappropriate cytokine profiles may be detrimental to the host.