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Mechanism of cyclosporin A-induced immunosuppression. Cyclosporin A inhibits receptor-mediated and non-receptor-mediated lymphokine production as well as interleukin-2-induced proliferation in cloned T lymphocytes

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Title: Mechanism of cyclosporin A-induced immunosuppression. Cyclosporin A inhibits receptor-mediated and non-receptor-mediated lymphokine production as well as interleukin-2-induced proliferation in cloned T lymphocytes
Authors: Harris, D. T., Kozumbo, W. J., Cerutti, P. A., Cerottini, J. C.
Publication Year: 2025
Collection: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
Subject Terms: Animals Calcium/metabolism Cell Division/drug effects Cyclosporins/*pharmacology Depression, Chemical Interleukin-2/biosynthesis/*pharmacology Lymphocyte Activation/*drug effects Lymphokines/biosynthesis Macrophage-Activating Factors Mice Receptors, Immunologic/metabolism Receptors, Interleukin-2 Receptors, Mitogen/*drug effects/metabolism T-Lymphocytes, Cytotoxic/*drug effects/immunology/metabolism
Description: The effects of cyclosporin A (CyA) on the activation processes of cloned murine cytotoxic T lymphocytes (CTL) have been examined. With the use of Day 7 resting cloned CTL it was possible to separate the functions of lymphokine production (macrophage-activating factor, MAF) and interleukin 2 (IL-2)-induced proliferation of these cells. The effect of CyA on each of these activities was analyzed independently. CyA was found to inhibit both receptor-mediated MAF production in response to stimulation with antigen and lectin and MAF production in response to non-receptor-mediated stimulation (by anti-Thy-1 antibodies, ionophore, and phorbol ester). Further, CyA was observed to inhibit the re-entry of these resting CTL into the cell cycle upon stimulation with IL-2. The effect of CyA on MAF production did not appear to be due to inhibition of the signal-transducing mechanism involved in this process (i.e., inositol lipid hydrolysis, calcium mobilization, and protein phosphorylation). The action of CyA on the IL-2-induced proliferation was not due to inhibition of IL-2 receptor expression or the binding of IL-2 to its receptor. Thus, CyA appeared to mediate its suppressive effects on MAF production and IL-2-induced proliferation through an action on some later step(s) in the signal pathways of these activities.
Document Type: article in journal/newspaper
Language: unknown
ISSN: 0008-8749
Relation: Cellular Immunology; https://iris.unil.ch/handle/iris/99364; serval:BIB_5A74B04D9DD4; A1987K369200010; 3115596
DOI: 10.1016/0008-8749(87)90296-6
Availability: https://iris.unil.ch/handle/iris/99364
https://doi.org/10.1016/0008-8749(87)90296-6
Accession Number: edsbas.8167F519
Database: BASE
Description
Abstract:The effects of cyclosporin A (CyA) on the activation processes of cloned murine cytotoxic T lymphocytes (CTL) have been examined. With the use of Day 7 resting cloned CTL it was possible to separate the functions of lymphokine production (macrophage-activating factor, MAF) and interleukin 2 (IL-2)-induced proliferation of these cells. The effect of CyA on each of these activities was analyzed independently. CyA was found to inhibit both receptor-mediated MAF production in response to stimulation with antigen and lectin and MAF production in response to non-receptor-mediated stimulation (by anti-Thy-1 antibodies, ionophore, and phorbol ester). Further, CyA was observed to inhibit the re-entry of these resting CTL into the cell cycle upon stimulation with IL-2. The effect of CyA on MAF production did not appear to be due to inhibition of the signal-transducing mechanism involved in this process (i.e., inositol lipid hydrolysis, calcium mobilization, and protein phosphorylation). The action of CyA on the IL-2-induced proliferation was not due to inhibition of IL-2 receptor expression or the binding of IL-2 to its receptor. Thus, CyA appeared to mediate its suppressive effects on MAF production and IL-2-induced proliferation through an action on some later step(s) in the signal pathways of these activities.
ISSN:00088749
DOI:10.1016/0008-8749(87)90296-6