| First Author | Lebel MÈ | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 3734 |
| PubMed ID | 32709894 | Mgi Jnum | J:292065 |
| Mgi Id | MGI:6447122 | Doi | 10.1038/s41467-020-17544-3 |
| Citation | Lebel ME, et al. (2020) Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates. Nat Commun 11(1):3734 |
| abstractText | Medullary thymic epithelial cells (mTEC) contribute to the development of T cell tolerance by expressing and presenting tissue-restricted antigens (TRA), so that developing T cells can assess the self-reactivity of their antigen receptors prior to leaving the thymus. mTEC are a heterogeneous population of cells that differentially express TRA. Whether mTEC subsets induce distinct autoreactive T cell fates remains unclear. Here, we establish bacterial artificial chromosome (BAC)-transgenic mouse lines with biased mTEC(lo) or mTEC(hi) expression of model antigens. The transgenic lines support negative selection of antigen-specific thymocytes depending on antigen dose. However, model antigen expression predominantly by mTEC(lo) supports TCRalphabeta(+) CD8alphaalpha intraepithelial lymphocyte development; meanwhile, mTEC(hi)-restricted expression preferentially induces Treg differentiation of antigen-specific cells in these models to impact control of infectious agents and tumor growth. In summary, our data suggest that mTEC subsets may have a function in directing distinct mechanisms of T cell tolerance. |
