First Author | Bilate AM | Year | 2020 |
Journal | Immunity | Volume | 53 |
Issue | 5 | Pages | 1001-1014.e20 |
PubMed ID | 33022229 | Mgi Jnum | J:306893 |
Mgi Id | MGI:6706714 | Doi | 10.1016/j.immuni.2020.09.003 |
Citation | Bilate AM, et al. (2020) T Cell Receptor Is Required for Differentiation, but Not Maintenance, of Intestinal CD4(+) Intraepithelial Lymphocytes. Immunity 53(5):1001-1014.e20 |
abstractText | The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneous T cell population with cytotoxic and regulatory properties, which can be acquired at the epithelial layer. However, the role of T cell receptor (TCR) in this process remains unclear. Single-cell transcriptomic analyses revealed distinct clonal expansions between cell states, with CD4(+)CD8alphaalpha(+) IELs being one of the least diverse populations. Conditional deletion of TCR on differentiating CD4(+) T cells or of major histocompatibility complex (MHC) class II on intestinal epithelial cells prevented CD4(+)CD8alphaalpha(+) IEL differentiation. However, TCR ablation on differentiated CD4(+)CD8alphaalpha(+) IELs or long-term cognate antigen withdraw did not affect their maintenance. TCR re-engagement of antigen-specific CD4(+)CD8alphaalpha(+) IELs by Listeria monocytogenes did not alter their state but correlated with reduced bacterial invasion. Thus, local antigen recognition is an essential signal for differentiation of CD4(+) T cells at the epithelium, yet differentiated IELs are able to preserve an effector program in the absence of TCR signaling. |