CTLA-4 can function as a negative regulator of T cell activation

Theresa L. Walunas*, Deborah J. Lenschow, Christina Y. Bakker, Peter S. Linsley, Gordon J. Freeman, Jonathan M. Green, Craig B. Thompson, Jeffrey A. Bluestone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1581 Scopus citations

Abstract

CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs Inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
JournalImmunity
Volume1
Issue number5
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Infectious Diseases

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