Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen

Nature. 1989 Nov 30;342(6249):559-61. doi: 10.1038/342559a0.


The crucial role of the thymus in immunological tolerance has been demonstrated by establishing that T cells are positively selected to express a specificity for self major histocompatibility complex (MHC), and that those T cells bearing receptors potentially reactive to self antigen fragments, presumably presented by thymic MHC, are selected against. The precise mechanism by which tolerance is induced and the stage of T-cell development at which it occurs are not known. We have now studied T-cell tolerance in transgenic mice expressing a T-cell receptor with double specificities for lymphocytic choriomeningitis virus (LCMV)-H-2Db and for the mixed-lymphocyte stimulatory (MIsa) antigen. We report that alpha beta TCR transgenic mice tolerant to LCMV have drastically reduced numbers of CD4+CD8+ thymocytes and of peripheral T cells carrying the CD8 antigen. By contrast, tolerance to MIsa antigen in the same alpha beta TCR transgenic MIsa mice leads to deletion of only mature thymocytes and peripheral T cells and does not affect CD4+CD8+ thymocytes. Thus the same transgenic TCR-expressing T cells may be tolerized at different stages of their maturation and at different locations in the thymus depending on the antigen involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface / immunology*
  • Antigens, Viral / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens
  • Cytotoxicity, Immunologic
  • Immune Tolerance*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Transgenic / immunology*
  • Minor Lymphocyte Stimulatory Antigens
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*


  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • Antigens, Viral
  • CD8 Antigens
  • Minor Lymphocyte Stimulatory Antigens