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Cytotoxic T lymphocyte‐associated antigen‐4 inhibits integrin‐mediated stimulation
Author(s) -
Gatta Lucia,
Calviello Gabriella,
Di Nicuolo Fiorella,
Pace Luigia,
Ubaldi Vanessa,
Doria Gino,
Pioli Claudio
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01493.x
Subject(s) - cd28 , cytotoxic t cell , t cell receptor , antigen , t cell , lymphocyte function associated antigen 1 , cd3 , biology , microbiology and biotechnology , t lymphocyte , immunology , ctla 4 , antigen presenting cell , monoclonal antibody , cd8 , antibody , immune system , in vitro , biochemistry
Summary 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 Ca 2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA‐4 engagement negatively affects Ca 2+ 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.