Role of interleukin 12 and costimulators in T cell anergy in vivo

Luk Van Parijs, Victor L. Perez, Andre Biuckians, Robert G. Maki, Cheryl A. London, Abul K. Abbas

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The induction oft cell anergy in vivo is thought to result from antigen recognition in the absence of co-stimulation and inflammation, and is associated with a block in T cell proliferation and Th1 differentiation. Here we have examined the role of interleukin (IL)-12, a potent inducer of Th1 responses, in regulating this process. T cell tolerance was induced by the administration of protein antigen without adjuvant in normal mice, and in recipients of adoptively transferred T cells from T cell receptor transgenic mice. The administration of IL-12 at the time of tolerance induction stimulates Th1 differentiation, but does not promote antigen-specific T cell proliferation. Conversely, inhibiting CTLA-4 engagement during anergy induction reverses the block in T cell proliferation, but does not promote full Th1 differentiation. T cells exposed to tolerogenic antigen in the presence of both IL-12 and anti-CTLA-4 antibody are not anergized, and behave identically to T cells which have encountered immunogenic antigen. These results suggest that two processes contribute to the induction of anergy in vivo; CTLA-4 engagement, which leads to a block in the ability oft cells to proliferate to antigen, and the absence of a prototypic inflammatory cytokine, IL-12, which prevents the differentiation oft cells into Th1 effector cells. The combination of IL-12 and anti-CTLA-4 antibody is sufficient to convert a normally tolerogenic stimulus to an immunogenic one.

Original languageEnglish (US)
Pages (from-to)1119-1128
Number of pages10
JournalJournal of Experimental Medicine
Volume186
Issue number7
DOIs
StatePublished - Oct 6 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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