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

Lucia Gatta, Gabriella Calviello, Fiorella Di Nicuolo, Luigia Pace, Vanessa Ubaldi, Gino Doria, Claudio Pioli

Research output: Contribution to journalArticle


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. PLCγ1 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.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
Issue number2
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Immunology

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    Gatta, L., Calviello, G., Di Nicuolo, F., Pace, L., Ubaldi, V., Doria, G., & Pioli, C. (2002). Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation. Immunology, 107(2), 209-216.