CrmA Expression in T Lymphocytes of Transgenic Mice Inhibits CD95 (Fas/APO-1)-transduced Apoptosis, but Does Not Cause Lymphadenopathy or Autoimmune Disease

EMBO J. 1996 Oct 1;15(19):5167-76.

Abstract

The cysteine protease interleukin-1beta converting enzyme (ICE) is implicated as an effector of apoptosis in mammalian cells. Proteolytic activity of ICE can be blocked in vitro by the cytokine response modifier A (crmA), a serpin-like protease inhibitor encoded by cowpox virus. Here we show that CD2 enhancer-driven expression of crmA in T lymphocytes of transgenic mice (CD2-crmA mice) reduces CD95 (Fas/APO-1)-transduced apoptosis in vitro to the level seen in CD95-deficient mutant lpr mice, but does not protect against gamma-radiation or corticosteroid-induced cell death. Unlike lpr mice, CD2-crmA transgenic mice developed neither T cell hyperplasia nor serum autoantibodies. These results provide evidence that the phenotype of lpr mice is not simply due to failure of CD95 to trigger T cell apoptosis mediated by ICE.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Autoantibodies / blood
  • CD2 Antigens / genetics
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Enhancer Elements, Genetic / genetics
  • Gamma Rays
  • Gene Expression
  • Glucocorticoids / pharmacology
  • Humans
  • Lymph Nodes / chemistry
  • Lymph Nodes / cytology
  • Lymphocyte Activation
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Serpins / genetics
  • Serpins / physiology*
  • Spleen / chemistry
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thy-1 Antigens / analysis
  • Thymus Gland / chemistry
  • Thymus Gland / cytology
  • Thymus Gland / radiation effects
  • Viral Proteins*
  • fas Receptor / analysis
  • fas Receptor / physiology*

Substances

  • Autoantibodies
  • CD2 Antigens
  • Glucocorticoids
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Serpins
  • Thy-1 Antigens
  • Viral Proteins
  • fas Receptor
  • Dexamethasone
  • interleukin-1beta-converting enzyme inhibitor