bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship

Cell. 1991 Nov 29;67(5):889-99. doi: 10.1016/0092-8674(91)90362-3.

Abstract

Early death is the fate of most developing T lymphocytes. Because bcl-2 can promote cell survival, we tested its impact in mice expressing an E mu-bcl-2 transgene within the T lymphoid compartment. The T cells showed remarkably sustained viability and some spontaneous differentiation in vitro. They also resisted killing by lymphotoxic agents. Although total T cell numbers and the rate of thymic involution were unaltered, the response to immunization was enhanced, consistent with reduced death of activated T cells. No T cells reactive with self-superantigens appeared in the lymph nodes, but an excess was found in the thymus. These observations, together with previous findings on B cells, suggest that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / analysis
  • Azides / pharmacology
  • Cell Death*
  • Cell Differentiation
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Crosses, Genetic
  • Dexamethasone / pharmacology
  • Female
  • Gamma Rays
  • Ionomycin / pharmacology
  • Kinetics
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • Sodium Azide
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / radiation effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology

Substances

  • Antigens, Surface
  • Azides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Ionomycin
  • Dexamethasone
  • Sodium Azide
  • Protein-Tyrosine Kinases
  • Tetradecanoylphorbol Acetate