Transcriptional cascades in the CD4/CD8 lineage choice

描述(申请人提供)：胸腺细胞成熟涉及多个 世系决定。决定成为成熟的CD4+辅助T细胞与CD8+ 杀伤T细胞是由通过T细胞接收到的信号的积分决定的 细胞受体和CD4、CD8辅助受体。发育中的命运受体， Noch，也被认为与CD4和CD8的血统承诺有关。这个 对这些整合信号的解释是转录的激活 因素，然后协调共同前体的不同发展， CD4+CD8+胸腺细胞，转化为辅助性T细胞或杀伤T细胞。有一个号码 在谱系中可能具有功能的候选转录因子 承诺和成熟。它们在胸腺细胞DP向SP转化过程中的作用 他们随后的转录级联将直接在这里讨论 建议以及鉴定更多胸腺细胞发育的方法 调解人。 目的1：评估转录因子和介体的作用 CD_4与CD_8谱系之间的关系 在胸腺器官培养中诱导CD4或CD8成熟。目标2：确定 TCR和Notch诱导的其他下游介体和靶点的差异 展示和微阵列分析。

DESCRIPTION (provided by applicant): Thymocyte maturation involves a number of lineage decisions. The decision to become mature CD4+ helper T cells vs. CD8+ killer T cells is determined by the integration of signals received through T cell receptors and CD4 and CD8 coreceptors. The developmental fate receptor, Notch, has also been implicated in CD4 vs. CD8 lineage commitment. The interpretation of these integrated signals is the activation of transcription factors, which then orchestrate differential development of a common precursor, CD4+CD8+ thymocytes, into either helper or killer T cells. There are a number of candidate transcription factors with possible functions in lineage commitment and maturation. Their roles during thymocyte DP to SP transition and their subsequent transcriptional cascades will be directly addressed in this proposal along with methods of identifying more thymocyte developmental mediators. Aim 1: Evaluate the roles of transcription factors and mediators implicated in the CD4 vs. CD8 lineage decision by following their kinetics during the induction of CD4 or CD8 maturation in thymic organ cultures. Aim 2: Identify other TCR- and Notch-induced downstream mediators and targets by differential display and microarray analysis.