Critical role for the common cytokine receptor gamma chain in intrathymic and peripheral T cell selection

J Exp Med. 1996 Mar 1;183(3):1111-8. doi: 10.1084/jem.183.3.1111.

Abstract

The common cytokine receptor gamma chain (gammac), which is a functional subunit of the receptors for interleukins (IL)-2, -4, -7, -9, and -15, plays an important role in lymphoid development. Inactivation of this molecule in mice leads to abnormal T cell lymphopoiesis characterized by thymic hypoplasia and reduced numbers of peripheral T cells. To determine whether T cell development in the absence of gammac is associated with alterations of intrathymic and peripheral T cell selection, we have analyzed gammac-deficient mice made transgenic for the male-specific T cell receptor (TCR) HY (HY/gammac- mice). In HY/gammac- male mice, negative selection of autoreactive thymocytes was not diminished; however, peripheral T cells expressing transgenic TCR-alpha and -beta chains (TCR-alphaT/betaT) were absent, and extrathymic T cell development was completely abrogated. In HY/gammac- female mice, the expression of the transgenic TCR partially reversed the profound thymic hypoplasia observed in nontransgenic gammac- mice, generating increased numbers of thymocytes in all subsets, particularly the TCR-alphaT/betaT CD8+ single-positive thymocytes. Despite efficient positive selection, however, naive CD8+ TCR-alphaT/betaT T cells were severely reduced in the peripheral lymphoid organs of HY/gammac- female mice. These results not only underscore the indispensible role of gammac in thymocyte development, but also demonstrate the critical role of gammac in the maintenance and/or expansion of peripheral T cell pools.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Crosses, Genetic
  • Duodenum / immunology
  • Female
  • Flow Cytometry
  • Lymphocyte Activation
  • Macromolecular Substances
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Cytokine / chemistry*
  • Receptors, Cytokine / immunology*
  • Receptors, Interleukin-2 / genetics
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Macromolecular Substances
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cytokine
  • Receptors, Interleukin-2