Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation.
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.
Gatta
Lucia
L
Section of Toxicology and Biomedicine, ENEA C. R. Casaccia, Via Anguillarse 301, 00060 Rome, Italy.
Calviello
Gabriella
G
Di Nicuolo
Fiorella
F
Pace
Luigia
L
Ubaldi
Vanessa
V
Doria
Gino
G
Pioli
Claudio
C
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002118:Calcium / Q000378:metabolism; D018796:Immunoconjugates; D016023:Integrins / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D051966:Phospholipase C gamma; D010766:Phosphorylation; D010738:Type C Phospholipases / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D016023:Integrins; D007376:Interleukin-2; D007527:Isoenzymes; D016169:Lymphocyte Function-Associated Antigen-1; D000069594:Abatacept; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium