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The influence of cyclosporin A on the alternative pathways of human T cell activation in vitro
Author(s) -
Bloemena Elisabeth,
Van Oers Rien H. J.,
Weinreich Stephanie,
StilmaMeinesz Anneke P.,
Schellekens Peter T. H. A.,
Van Lier René A. W.
Publication year - 1989
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830190524
Subject(s) - cd28 , cd3 , biology , monoclonal antibody , intracellular , t cell , mechanism of action , microbiology and biotechnology , stimulation , signal transduction , phorbol , receptor , in vitro , antibody , biochemistry , protein kinase c , immunology , cytotoxic t cell , antigen , cd8 , endocrinology , immune system
Abstract To gain further insight into the mechanism of action of the immunosuppressant cyclosporin A (CyA), we investigated the influence of CyA on proliferative responses of human T lymphocytes, induced via different membrane molecules. As was previously shown, activation of T cells via the T cell receptor (Ti)/CD3 complex with an anti‐CD3 monoclonal antibody was inhibited by CyA. Likewise, triggering of T lymphocytes via the alternative, CD2(T11)‐mediated pathway of activation was strongly inhibited. In contrast, responses induced by phorbol myristate 13‐acetate (PMA; 100 ng/ml) or the combination of an anti‐CD28 monoclonal antibody and a suboptimal concentration of PMA (1 ng/ml) were found to be insensitive to CyA. CyA‐induced inhibition of both anti‐CD3 and anti‐CD2‐mediated proliferation could not be reversed by addition of either PMA (1 ng/ml) or anti‐CD28. An increase in the intracellular free Ca 2+ concentration ([Ca 2+ ] i ) is an early event observed after stimulation of T cells via CD3 or CD2, whereas stimulation with PMA and anti‐CD28 does not lead to a rise in [Ca 2+ ] i This suggests that the inhibitory action of CyA is related to Ca 2+ ‐dependent signaling pathways. Since we observed that CyA does not interfere with anti‐CD3‐ or anti‐CD2‐induced increases of [Ca 2+ ] i , our data suggest that CyA‐mediated inhibition is related to a later event in these intracellular signaling pathways.