B7-independent inhibition of T cells by CTLA-4

Shunsuke Chikuma, Abul K. Abbas, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

CTLA-4 is an inhibitory molecule that regulates T cell expansion and differentiation. CTLA-4 binding to B7-1/B7-2 is believed to be crucial for its inhibitory signal both by competing for CD28 binding to the same ligands and aggregating CTLA-4 to deliver negative signals. In this study, we demonstrate that B7 binding is not essential for CTLA-4 activity. CTLA-4 knockout T cells are hyperresponsive compared with wild-type T cells in B7-free settings. Expression of a B7-nonbinding CTLA-4 mutant inhibited T cell proliferation, cytokine production, and TCR-mediated ERK activation in otherwise CTLA-4-deficient T cells. Finally, transgenic expression of the ligand-nonbinding CTLA-4 mutant delayed the lethal lymphoproliferation observed in CTLA-4-deficient mice. These results suggest that ligand binding is not essential for the CTLA-4 function and supports an essential role for CTLA-4 signaling during T cell activation.

Original languageEnglish
Pages (from-to)177-181
Number of pages5
JournalJournal of Immunology
Volume175
Issue number1
DOIs
Publication statusPublished - 2005 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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