Cyclosporine does not prevent cytoplasmic calcium changes associated with lymphocyte activation

Abstract

The recent development of fluorescent reagents that are sensitive to calcium ions has made it possible to quantitate cytoplasmic calcium levels of lymphocytes. The cytoplasmic calcium concentration more than doubles within the first few minutes following lymphocyte stimulation. Here I show that it is likely that this increase in calcium is an absolute requirement for mitogenic commitment. Brief exposure of T cells to concanavalin A (Con A) is sufficient to stimulate cell division, provided that extracellular calcium ions are available to the cells at the time of exposure to mitogen--no mitogenesis occurs if extracellular calcium is below 10(-5)M. Commitment to mitosis requires both Con A acting at the cell surface and a source of extracellular calcium, so it follows that the plasma membrane is implicated in the control of cytoplasmic calcium changes. The lipid-soluble nature of cyclosporine (Cys) results in the partitioning of this drug into the plasma membrane of lymphocytes; the possibility arises that Cys might inhibit lymphocyte activation by perturbing membrane structure so as to alter regulatory fluxes in cytoplasmic calcium. Experiments reported here show that early changes in cytoplasmic calcium levels of activated T cells occur normally in the presence of Cys.