In:
Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-07-24)
Abstract:
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 TCRαβ + CD8αα intraepithelial lymphocyte development; meanwhile, mTEC hi -restricted expression preferentially induces T reg 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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-020-17544-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2553671-0
Bookmarklink
