Antigenic specificities of intestinal CD4+Foxp3+ T cells.

在肠道中，表达Foxp3转录因子(Tregs)的调节性T细胞对 对共生抗原的适应性免疫反应的调节。Tregs的区别在于 胸腺(TTregs)或从幼稚的外周Foxp3-T细胞(PTregs)转化而来。目前尚不清楚 TTregs和pTregs在维持肠道功能中是否有多余或互补的作用 动态平衡。我们的长期目标是了解肠道内的动态平衡 取决于pTregs和tTregs，以及它们的TCR曲目如何因暴露于 抗生素。我们的中心假设是tTregs的克隆扩张和选择性营养是 对维持肠道平衡至关重要。为了检验我们的假设，我们提出了两个具体目标。 首先，我们将对CNS1突变小鼠肠道粘膜Tregs上的TCRs进行表征 PTregs，但tTregs正常。此外，在这些小鼠中，CD4+T细胞表达半多样化 TCRs和激活的Tregs表达绿色荧光蛋白(GFP)。我们 假设在这些小鼠中，粘膜tTregs将控制肠道幼稚T细胞和效应性T细胞， TTregs表达的TCRs可以针对共生抗原。第二，我们将 研究生命早期的抗生素治疗如何永久性地改变微生物区系和 肠道Tregs的克隆多样性。我们假设微生物多样性的变化 新生儿接触抗生素引起的菌群永久性地改变了肠道细菌的种类。

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 activated Tregs express green fluorescent protein (GFP). We hypothesize that in these mice mucosal tTregs will control intestinal naïve 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.