Antigenic specificities of intestinal CD4+Foxp3+ T cells.

在肠道中，表达Foxp 3转录因子（TCF 3）的调节性T细胞对于 调节机体对抗原的适应性免疫反应。Tumor differentiation在 胸腺细胞（tTcells）或从幼稚外周Foxp 3- T细胞（pTcells）转化而来。 如果tTdR和pTdR在维持肠功能中具有冗余或互补作用， 体内平衡我们的长期目标是了解肠道内的稳态平衡 这取决于pT 3和tT 4，以及它们的TCR库如何通过暴露于 抗生素我们的中心假设是，克隆扩张和选择性营养作用的tT 对维持肠道平衡至关重要为了验证我们的假设，我们提出了两个具体的目标。 首先，我们将描述缺乏TCRs的CNS 1 mut小鼠肠粘膜TCRs的特征。 pT 3，但tT 4正常。此外，在这些小鼠中，CD 4 + T细胞表达半多样性。 TCR库和活化的TCR表达绿色荧光蛋白（GFP）。我们 假设在这些小鼠中，粘膜tT细胞将控制肠道幼稚和效应T细胞， 并且由tTCRs表达的TCR可以特异性针对免疫抗原。二是 研究生命早期抗生素治疗如何永久改变微生物植物群， 肠上皮细胞克隆多样性。我们假设微生物多样性的变化 新生儿暴露于抗生素诱导的植物群永久性改变了肠道菌群。

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.