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 Mis(a) antigens in vivo leads to specific tolerance and disappearance of Mis(a)-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.