Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity

Cell. 1990 Dec 21;63(6):1249-56. doi: 10.1016/0092-8674(90)90420-j.


The mechanism by which T lymphocytes are tolerized to self or foreign antigens is still controversial. Clonal deletion is the major mechanism of tolerance for immature thymocytes; for mature T cells, tolerance is considered to reflect anergy rather than deletion, and to be a consequence of defective presentation of antigen. This paper documents a novel form of tolerance resulting when mature T cells encounter antigen in immunogenic form. Evidence is presented that exposure of mature T cells to Mlsa antigens in vivo leads to specific tolerance and disappearance of Mlsa-reactive V beta 6+ T cells. Surprisingly, the clonal elimination of V beta 6+ cells is preceded by marked expansion of these cells. Thus, tolerance induction can be the end result of a powerful immune response. These data raise important questions concerning the relationship of tolerance and memory.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • CD4 Antigens / immunology
  • CD8 Antigens
  • Crosses, Genetic
  • Flow Cytometry
  • Immune Tolerance*
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred Strains
  • Receptors, Antigen, T-Cell / analysis
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology


  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell