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Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation.
- 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.
- Subjects :
- Abatacept
Animals
Antigens, CD
CD28 Antigens immunology
CD3 Complex immunology
CD4-Positive T-Lymphocytes metabolism
CTLA-4 Antigen
Calcium metabolism
Interleukin-2 biosynthesis
Isoenzymes metabolism
Lymphocyte Function-Associated Antigen-1 immunology
Mice
Mice, Inbred C57BL
Phospholipase C gamma
Phosphorylation
Type C Phospholipases metabolism
Antigens, Differentiation immunology
CD4-Positive T-Lymphocytes immunology
Immunoconjugates
Integrins immunology
Lymphocyte Activation immunology
Subjects
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