The common cytokine receptor gamma chain controls survival of gamma/delta T cells

J Exp Med. 1997 Oct 20;186(8):1277-85. doi: 10.1084/jem.186.8.1277.

Abstract

We have investigated the role of common gamma chain (gamma c)-signaling pathways for the development of T cell receptor for antigen (TCR)-gamma/delta T cells. TCR-gamma/delta-bearing cells were absent from the adult thymus, spleen, and skin of gamma c-deficient (gamma c-) mice, whereas small numbers of thymocytes expressing low levels of TCR-gamma/delta were detected during fetal life. Recent reports have suggested that signaling via interleukin (IL)-7 plays a major role in facilitating TCR-gamma/delta development through induction of V-J (variable-joining) rearrangements at the TCR-gamma locus. In contrast, we detected clearly TCR-gamma rearrangements in fetal thymi from gamma c- mice (which fail to signal in response to IL-7) and reduced TCR-gamma rearrangements in adult gamma c thymi. No gross defects in TCR-delta or TCR-beta rearrangements were observed in gamma c- mice of any age. Introduction of productively rearranged TCR V gamma 1 or TCR V gamma 1/V delta 6 transgenes onto mice bearing the gamma c mutation did not restore TCR-gamma/delta development to normal levels suggesting that gamma c-dependent pathways provide additional signals to developing gamma/delta T cells other than for the recombination process. Bcl-2 levels in transgenic thymocytes from gamma c- mice were dramatically reduced compared to gamma c+ transgenic littermates. We favor the concept that gamma c-dependent receptors are required for the maintenance of TCR-gamma/delta cells and contribute to the completion of TCR-gamma rearrangements primarily by promoting survival of cells committed to the TCR-gamma/delta lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / genetics
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / genetics
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / physiology*
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology*
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / physiology

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Cytokine