Cyclosporin A (Sandimmun) modulates the Ca2+ uptake of mitogen-stimulated lymphocytes

Incubation of murine spleen cells, or enriched T-cell populations, with the T-cell-dependent polyclonal mitogens Con-A or PHA resulted in a dose-dependent increase in 45Ca2+ uptake. This effect was observed after a delay of about 30 to 60 min, reached a maximum after 2-4 h and lasted up to 6 h. Similarly, the calcium ionophore A23187 caused an increased Ca2+ uptake, although this was faster, occurring within a few minutes, reaching a maximum at 15 min and lasting for about 2-4 h. No change in Ca2+ uptake was observed using a specific B-cell mitogen (lipopolysaccharide) or B-cell preparations. Nifedipine, a calcium channel-blocking agent, inhibited activation of lymphocytes in a primary immune response (mixed lymphocyte reaction and formation of plaque forming cells in vitro) but was unable to interfere with proliferating cell lines or a secondary immune response. Incubation of Con-A-activated lymphocytes with the immunosuppressive agent CS-A caused an additional increase in calcium uptake, whereas no change in calcium uptake was observed when resting lymphocytes or B-cells activated by LPS were incubated with cyclosporin. A similar potentiation of Con-A-induced calcium uptake was seen with hydrocortisone, but not with cytostatic agents or anti-lymphocyte serum. Submaximal calcium uptake induced by the ionophore A23187 was potentiated by CS-A and hydrocortisone as well as by cytostatic agents and ALS.