Identification of pre- and postselection TCRalphabeta+ intraepithelial lymphocyte precursors in the thymus

Immunity. 2006 Oct;25(4):631-41. doi: 10.1016/j.immuni.2006.08.018.

Abstract

The immune system preserves and makes use of autoreactive lymphocytes with specialized functions. Here we showed that one of these populations, CD8alphaalpha(+)TCRalphabeta(+) intestinal intraepithelial lymphocytes (IELs), arose from a unique subset of double-positive thymocytes. This subset of cells was precommitted to preferentially give rise to CD8alphaalpha(+)TCRalphabeta(+) IELs, but they required exposure to self-agonist peptides. The agonist-selected TCRalphabeta(+) thymocytes are CD4 and CD8 double-negative, and their final maturation, including the induction of CD8alphaalpha expression, appeared to occur only after thymus export in the IL-15-rich environment of the gut. These developmental steps, including precommitment of immature thymocytes, TCR-mediated agonist selection, and postthymic differentiation promoted by cytokines, define a unique pathway for the generation of CD8alphaalpha(+)TCRalphabeta(+) IEL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Cell Differentiation
  • Cytokines / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred Strains
  • Phenotype
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta