Divergent effects of cyclosporine A on interferon- and mitogen-induced Ly-6A antigen suggest autocrine regulation of Ly-6A expression in activated T cells.
The murine Ly-6A cell surface antigen is normally present on a minor subset of mature T cells. This marker has been shown to become highly expressed on mitogen-activated T cells. We found that expression of Ly-6A is also markedly increased in resting T cells by incubation with IFN-alpha/beta or IFN-gamma. Here, we compared the effect of the immunosuppressant cyclosporine A (CsA) on Ly-6A induction by IFN and concanavalin A (Con A). The augmentation of Ly-6A expression produced by treatment of T cells with IFN-alpha/beta or IFN-gamma was found not to be affected by CsA concentrations up to 2 micrograms/ml. In contrast, at doses as low as 50 ng/ml, CsA prevented the enhancement of Ly-6A expression in Con A-treated T-cell cultures. Culture supernatant transfer experiments were performed to further explore this effect of CsA. It was found that supernatants from Con A-activated T cells enhanced Ly-6A expression in resting T cells. This activity could be neutralized with an anti-IFN-gamma monoclonal antibody. Supernatants from T cells treated with Con A in presence of CsA lacked Ly-6A-enhancing activity. Taken together, these data suggest that the inhibition by CsA of Ly-6A induction in Con A-treated T cells reflects the known inhibitory effects of the drug on IFN-gamma secretion. This may imply the existence in T cells of an autocrine circuit involving IFN-gamma and regulating Ly-6A expression.
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007372:Interferons / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000950:Antigens, Ly; D003524:Cyclosporins; D008934:Mitogens; D007371:Interferon-gamma; D007372:Interferons