Role of Bcl-2 in alpha beta T cell development in mice deficient in the common cytokine receptor gamma-chain: the requirement for Bcl-2 differs depending on the TCR/MHC affinity

J Immunol. 1999 Jan 15;162(2):782-90.

Abstract

Mice lacking the common cytokine receptor gamma-chain (gamma c) exhibit severely compromised T cell development, with diminished Bcl-2 expression in mature (CD4+ or CD8+) thymocytes and peripheral T cells. Enforced expression of Bcl-2 in these mice partially rescued alpha beta T cell development but not gamma delta T cell development. Transgenic expression of the OVA-specific DO11.10 (DO10) TCR also could modestly increase thymocyte numbers, and T cells expressing the transgenic TCR (KJ1-26+ T cells) were found in the periphery. Interestingly, the presence of KJ1-26+ T cells was dependent on the MHC background and was seen in the moderate affinity H-2d/d background but not in the higher affinity H-2d/b background in gamma c-deficient mice. In contrast, KJ1-26+ T cells exist in the periphery in both the H-2d/d and H-2d/b backgrounds in DO10 transgenic gamma c wild-type mice. These results suggest that the importance of gamma c-dependent signals for T cell development differs depending on the affinity of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greater effect on the development of gamma c-deficient T cells expressing the DO10 TCR in the high affinity H-2d/b background than in the H-2d/d background, suggesting that gamma c-dependent Bcl-2 expression influences T cell development in a TCR/MHC-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / biosynthesis
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Cycle / genetics
  • Cell Cycle / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Female
  • H-2 Antigens / genetics
  • H-2 Antigens / metabolism*
  • Histocompatibility Antigen H-2D
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / deficiency
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Cytokine / deficiency*
  • Receptors, Cytokine / genetics
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • Transgenes / immunology

Substances

  • CD3 Complex
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Cytokine
  • Receptors, Interleukin-2