A role for Fas in negative selection of thymocytes in vivo

J Exp Med. 1998 May 4;187(9):1427-38. doi: 10.1084/jem.187.9.1427.

Abstract

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1-100 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (</=1 microg) but not by high doses (100 microg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Clone Cells / immunology
  • Enterotoxins / immunology
  • Flow Cytometry
  • Immune Tolerance / immunology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Thymus Gland / physiology*
  • fas Receptor / physiology*

Substances

  • Antibodies, Monoclonal
  • Enterotoxins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • fas Receptor
  • enterotoxin B, staphylococcal
  • Ovalbumin