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

TitleCytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2002
AuthorsGatta, L., Calviello G., Di Nicuolo F., Pace L., Ubaldi V., Doria G., and Pioli Claudio
JournalImmunology
Volume107
Pagination209-216
ISSN00192805
Keywordsanimal cell, Animals, antigen expression, antigen function, Antigens, article, Calcium, calcium ion, calcium mobilization, CD, CD28, CD28 antigen, CD3, CD3 antigen, CD4-Positive T-Lymphocytes, cell adhesion molecule, cell stimulation, controlled study, cytokine release, cytotoxic T lymphocyte antigen 4, Differentiation, Immunoconjugates, Inbred C57BL, integrin, Integrins, interleukin 2, Interleukin-2, Isoenzymes, lymphocyte activation, lymphocyte function associated antigen 1, Lymphocyte Function-Associated Antigen-1, Mice, Monoclonal antibody, mouse, nonhuman, Phospholipase C, Phospholipase C gamma, Phosphorylation, priority journal, transcription factor NFAT
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. 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.

Notes

cited By 10

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0036413437&doi=10.1046%2fj.1365-2567.2002.01493.x&partnerID=40&md5=c57b79a9c5184e7e446e224498b7282c
DOI10.1046/j.1365-2567.2002.01493.x
Citation KeyGatta2002209