B7-independent inhibition of T cells by CTLA-4

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

Research output: Contribution to journalArticle

49 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
Publication statusPublished - 2005 Jul 1
Externally publishedYes

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T-Lymphocytes
Ligands
Cell Differentiation
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Chikuma, S., Abbas, A. K., & Bluestone, J. A. (2005). B7-independent inhibition of T cells by CTLA-4. Journal of Immunology, 175(1), 177-181.

B7-independent inhibition of T cells by CTLA-4. / Chikuma, Shunsuke; Abbas, Abul K.; Bluestone, Jeffrey A.

In: Journal of Immunology, Vol. 175, No. 1, 01.07.2005, p. 177-181.

Research output: Contribution to journalArticle

Chikuma, S, Abbas, AK & Bluestone, JA 2005, 'B7-independent inhibition of T cells by CTLA-4', Journal of Immunology, vol. 175, no. 1, pp. 177-181.
Chikuma S, Abbas AK, Bluestone JA. B7-independent inhibition of T cells by CTLA-4. Journal of Immunology. 2005 Jul 1;175(1):177-181.
Chikuma, Shunsuke ; Abbas, Abul K. ; Bluestone, Jeffrey A. / B7-independent inhibition of T cells by CTLA-4. In: Journal of Immunology. 2005 ; Vol. 175, No. 1. pp. 177-181.
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