Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement

Immunity. 1997 Apr;6(4):411-7. doi: 10.1016/s1074-7613(00)80284-8.


Studies of T cell anergy in vitro have led to the widely accepted view that anergy is induced by T cell antigen recognition without costimulation. We show that the induction of T cell anergy in vivo is due to an abortive T cell response that requires recognition of B7 molecules, since blocking B7 maintains T cells in an unactivated but functionally competent state. Furthermore, the induction of anergy is prevented by blocking CTLA-4, the inhibitory T cell receptor for B7 molecules. Thus, in vivo T cell anergy may be induced not because of a lack of costimulation, but as a result of specific recognition of B7 molecules by CTLA-4. In contrast, blocking CD28 on T cells prevents priming but not the induction of tolerance. Therefore, the outcome of antigen recognition by T cells is determined by the interaction of CD28 or CTLA-4 on the T cells with B7 molecules.

Publication types

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

MeSH terms

  • Abatacept
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation / metabolism*
  • Antigens, Differentiation / physiology
  • B7-1 Antigen / physiology
  • CTLA-4 Antigen
  • Epitopes / immunology
  • Immune Tolerance* / drug effects
  • Immunoconjugates*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Epitopes
  • Immunoconjugates
  • Abatacept