In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα⁺ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα⁺ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα⁺ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα⁺ IELs and CD4⁺ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα⁺ IELs and CD4⁺ derived T cell hybridomas suggesting that some of TCRαβCD8αα⁺ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4⁺ IELs and Foxp3CD4⁺ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3^CNS1 sufficient or Foxp3^CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα⁺ in small intestine expends in situ in response to changes in microbial flora.

中文翻译：

---

非规范招募的TCRαβCD8ααIEL识别微生物抗原。

在肠道中，上皮内T细胞（IEL）的各种子集对源自身体，饮食，共生和致病菌群的自身或非自身抗原作出反应。小肠中IEL的主要子集是TCRαβCD8αα ⁺细胞，它们来自表达自我反应性TCR的未成熟胸腺细胞。尽管大多数TCRαβCD8αα ⁺ IELs是胸腺来源的，但是它们的组成适应微生物菌群。在这里，使用高通量TCR测序，我们研究了TCRαβCD8αα ⁺ IELs的克隆多样性在暴露于共生来源的抗原后如何变化。我们发现CD8αα ⁺ IELs和CD4 ⁺T细胞表达相同的αβTCR，并且这种重叠平行于微生物菌群多样性的增加而升高。我们还发现，从小鼠小肠中分离出的机会病原体（金黄色葡萄球菌）会特异性激活CD8αα ⁺ IELs和CD4 ⁺衍生的T细胞杂交瘤，这表明某些具有微生物特异性的TCRαβCD8αα ⁺克隆具有胸腺来源。我们还报告说，小肠中的CD8ααCD4 ⁺ IELs和Foxp3CD4 ⁺ T细胞共享许多αβTCR，无论后来的子集是否从Foxp3 ^CNS1足够或Foxp3 ^CNS1中分离出来缺乏小鼠外周血Treg的小鼠。总体而言，我们的结果表明，小肠中TCRαβCD8αα ^+的库会根据微生物菌群的变化而原位消耗。