Cyclosporin elicits a non-responsive state and a shift in K+ fluxes in the early phase of activation of human lymphocytes with anti-CD3.
The effect of cyclosporin A on the initial phase of activation of human peripheral blood lymphocytes (PBL) by anti-CD3 was studied in a two-step incubation process. Cyclosporin A treatment in the initial phase of activation blocked the second phase activation of a cell population by anti-CD3, IL-2, or concanavalin A (ConA). In contrast, similar treatment with the calcium ionophore, ionomycin, enhanced the activation of anti-CD3. Only a marginal synergistic increase of intracellular [Ca2+] was elicited by cyclosporin A during anti-CD3 stimulation and this drug prevented activation-induced depolarization of lymphocytes by its ability to hyperpolarize cells. The hyperpolarization effect of cyclosporin A is related to the K+ flux but not the Na+ or Ca2+ flux and is unlikely to be mediated through calmodulin and protein kinase C. We postulate that the K+ flux-modulating ability of cyclosporin A renders T cells non-responsive in the initial phase of activation.
Aszalos
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A
Food and Drug Administration, Division of Pharmaceutical Research and Testing, Washington, DC 20204.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A; D016572:Cyclosporine; D011188:Potassium