DIFFERENTIAL ACTIVATION REQUIREMENTS OF CD4+ T CELLS

该项目的长期目标是进一步深入了解 调控CD4+T细胞发育、激活和功能的机制 在抗原特异性反应中细胞因子谱受限制的细胞。 该项目的目标是： 1.确定细胞因子在体内形成的精确机制 锁孔帽状血蓝蛋白(KLH)特异性记忆T细胞的类型 抗原提呈细胞及其激活状态 浓度，和APC共刺激分子影响这一发展。 2.分析细胞因子合成是如何在脑内差异调节的 不同品系的小鼠。 3.比较B细胞在淋巴因子发育中的作用 预激与未预激的CD4+T细胞的特征。 为了达到这些目的，我们已经建立了几种抗原特异性 跟随限制性淋巴因子特征发展的模型。我们 已经产生了大量的初步数据表明 KLH诱导的CD4+T细胞中IL-4的合成受 KLH在体外的浓度，并优先被抗原增强 被激活的B细胞的呈递。此外，我们还有几条线路 有证据表明淋巴因子合成的调节是 在不同品系的小鼠中存在差异，这是由于不同品系的小鼠在 抗原提呈细胞。最后，我们建立了准确和 细胞因子IL-2、IL-3和IL-4、IL-5、IL-6、 IL-10、干扰素-γ。 在对不同类型病原体的反应中-需要不同的 T细胞功能、T细胞亚群发育受限 细胞因子谱在调节细胞周期中起着至关重要的作用 免疫反应。了解调节 CD4+T细胞亚群的发展对理解和 治疗过敏、自身免疫性疾病、易感性等疾病 感染，或癌症，以及疫苗的开发，在这些情况下 细胞因子谱不适当的CD4+T细胞的发育可能是 对寄主有害的。

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.