The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice

Immunity. 1994 Aug;1(5):365-71. doi: 10.1016/1074-7613(94)90067-1.

Abstract

The role of a cell death-associated gene, fas, in T lymphocyte development and responses to antigen has been analyzed by breeding a transgenic T cell receptor specific for the 81-104 peptide of pigeon cytochrome c into fas-defective MRL-lpr/lpr and control MRL+/+ mice. Transgene-expressing T cells mature normally in both strains and populate peripheral lymphoid tissues in normal numbers. Mature CD4+ T cells from the lpr/lpr mice are resistant to suppression by high doses of antigen and to apoptotic cell death. In vivo administration of peptide antigen causes deletion of thymic T cells in both MRL-lpr/lpr and MRL+/+ strains. By contrast, antigen-induced deletion of peripheral T cells occurs in the MRL+/+ but not in the MRL-lpr/lpr strain. Therefore, the fas gene plays an essential role in activation-induced cell death in mature T lymphocytes, but not in the negative selection of immature cells in the thymus.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Surface / genetics*
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / ultrastructure*
  • Cellular Senescence
  • Gene Deletion
  • Gene Expression
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutation
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • fas Receptor

Substances

  • Antigens, Surface
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • fas Receptor