T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

Bilate, A. M.; London, M.; Castro, T. B. R.; Mesin, L.; Kongthong, S.; Harnagel, A.; Victora, G. D.; Mucida, D.

doi:10.1101/2020.06.04.134510

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bioRxiv · 10.1101/2020.06.04.134510

T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

Bilate, A. M.·London, M.·Castro, T. B. R.·Mesin, L.·Kongthong, S.·Harnagel, A.·Victora, G. D.·Mucida, D.

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Abstract

The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneous T cell population with cytotoxic and regulatory properties. Migrating peripheral CD4+ T cells, including regulatory (Treg) and conventional T cells (Tconv), acquire an IEL (CD4-IEL) program upon arrival at the epithelium. However, the specific role of the T cell receptor (TCR) in this process remains unclear. Single-cell TCR repertoire and transcriptomic analysis of intraepithelial CD4+ T cells revealed different extents of clonal expansion and TCR overlap between cell states; fully differentiated CD4-IELs from Tregs or Tconvs were the least diverse. Conditional deletion of TCR on differentiating CD4+ T cells or of MHCII on intestinal epithelial cells prevented CD4-IEL differentiation. However, TCR ablation on developed CD4-IELs did not affect their accumulation. These results indicate that local recognition of a limited set of antigens is an essential signal for the differentiation and adaptation of T cells to the epithelium.

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Bilate, A. M., London, M., Castro, T. B. R., Mesin, L., Kongthong, S., Harnagel, A., Victora, G. D., Mucida, D.. 2020-06-05. T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes. https://doi.org/10.1101/2020.06.04.134510

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