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

Victor L. Perez, Luk Van Parijs, Andre Biuckians, Xin Xiao Zheng, Terry B. Strom, Abul K. Abbas

Research output: Contribution to journalArticlepeer-review

647 Scopus citations

Abstract

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 87 molecules, since blocking 87 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 87 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 87 molecules.

Original languageEnglish
Pages (from-to)411-417
Number of pages7
JournalImmunity
Volume6
Issue number4
DOIs
StatePublished - 1 Apr 1997
Externally publishedYes

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