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Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation.

Authors :
Gatta L
Calviello G
Di Nicuolo F
Pace L
Ubaldi V
Doria G
Pioli C
Source :
Immunology [Immunology] 2002 Oct; Vol. 107 (2), pp. 209-16.
Publication Year :
2002

Abstract

The negative role exerted by cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the regulation of T-cell activity, as induced by T-cell receptor (TCR)/CD3 and CD28 costimulation, has been widely described. In the present work we investigated the role of CTLA-4 in the control of cell activation, as induced by costimulation of the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) in murine CD4+ T cells. Results show that CTLA-4 engagement inhibits interleukin-2 (IL-2) production, not only when induced by CD3/CD28 costimulation, but also when CD4+ T cells are costimulated by anti-CD3 and anti-LFA-1 monoclonal antibodies (mAbs). LFA-1 has been described to induce Ca2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA-4 engagement negatively affects Ca2+ mobilization and NF-AT activation, as induced by LFA-1 engagement alone. PLCgamma1 phosphorylation was also dampened within minutes after CTLA-4 engagement. Altogether these data indicate that through the control of signals induced by different receptors, CTLA-4 could be a global attenuator of T-cell activation.

Details

Language :
English
ISSN :
0019-2805
Volume :
107
Issue :
2
Database :
MEDLINE
Journal :
Immunology
Publication Type :
Academic Journal
Accession number :
12383200
Full Text :
https://doi.org/10.1046/j.1365-2567.2002.01493.x