Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.
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.
Webb
S
S
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Morris
C
C
Sprent
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens; D003433:Crosses, Genetic; D005434:Flow Cytometry; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell