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

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.

Pubmed ID: 2573841

Authors

  • Pircher H
  • B├╝rki K
  • Lang R
  • Hengartner H
  • Zinkernagel RM

Journal

Nature

Publication Data

November 30, 1989

Associated Grants

None

Mesh Terms

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