First Author | Wojciech L | Year | 2018 |
Journal | Sci Rep | Volume | 8 |
Issue | 1 | Pages | 10848 |
PubMed ID | 30022086 | Mgi Jnum | J:268715 |
Mgi Id | MGI:6271805 | Doi | 10.1038/s41598-018-29073-7 |
Citation | Wojciech L, et al. (2018) Non-canonicaly recruited TCRalphabetaCD8alphaalpha IELs recognize microbial antigens. Sci Rep 8(1):10848 |
abstractText | 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 TCRalphabetaCD8alphaalpha(+) cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRalphabetaCD8alphaalpha(+) IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRalphabetaCD8alphaalpha(+) IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8alphaalpha(+) IELs and CD4(+) T cells express identical alphabetaTCRs 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 CD8alphaalpha(+) IELs and CD4(+) derived T cell hybridomas suggesting that some of TCRalphabetaCD8alphaalpha(+) clones with microbial specificities have extrathymic origin. We also report that CD8alphaalphaCD4(+) IELs and Foxp3CD4(+) T cells from the small intestine shared many alphabetaTCRs, 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 TCRalphabetaCD8alphaalpha(+) in small intestine expends in situ in response to changes in microbial flora. |