Antigenic specificities of intestinal CD4+Foxp3+ T cells.

描述（由申请人提供）：在肠道中，表达Foxp3转录因子（Tregs）的调节性T细胞对于调节对共生抗原的适应性免疫反应至关重要。Tregs在胸腺中分化（tTregs）或从原始的外周Foxp3- T细胞（pTregs）转化而来。目前尚不清楚tTregs和pTregs在维持肠道稳态中是否有冗余或互补作用。我们的长期目标是了解肠道内的稳态平衡如何依赖于pTregs和tTregs，以及它们的TCR谱如何因暴露于抗生素而改变。我们的中心假设是，克隆扩增和选择性营养是维持肠道平衡所必需的。

DESCRIPTION (provided by applicant): In the intestine, regulatory T cells that express Foxp3 transcription factor (Tregs) are critical for the regulation of adaptive immune response to commensal antigens. Tregs differentiate in the thymus (tTregs) or convert from naive, peripheral Foxp3- T cells (pTregs).It is currently unclear if tTregs and pTregs have redundant or complimentary role in maintenance of intestinal homeostasis. Our long term goal is to understand how the homeostatic balance in the intestine depends on pTregs and tTregs, and how their TCR repertoires can change by exposure to antibiotics. Our central hypothesis is that clonal expansions and selective trophism of tTregs are essential to sustain intestinal equilibrium. To test our hypothesis we propose two specific aims. First we will characterize TCRs on mucosal Tregs in the intestine of CNS1mut mice that lack pTregs but have normal tTregs. In addition, in these mice CD4+ T cells express semi diverse repertoire of TCRs and all Tregs are labeled with green fluorescent protein (GFP). We hypothesize that in these mice mucosal tTregs will control intestinal na�ve and effector T cells, and that TCRs expressed by tTregs can be specific to commensal antigens. Second, we will investigate how antibiotic treatment early in life can permanently change microbial flora and clonal diversity of intestinal Tregs. We hypothesize that changes in the diversity for microbial flora induced by neonatal exposure to antibiotics permanently alter repertoire of intestinal tTregs.