Interference of cyclosporin with lymphocyte activation: blockage of the mitogen-induced increases of lysosomal and mitochondrial activities.

Abstract

Mouse lymphocytes were activated by a mitogenic dose of concanavalin A and analysed by flow cytometry to monitor the increases of mitochondrial activity (using rhodamine 123 as probe) and of lysosomal activity (using euchrysin [acridine orange] as probe). Cyclosporin A-treated lymphocytes were not capable of responding to concanavalin A in the same way as untreated lymphocytes: both the increased uptakes of rhodamine 123 by mitochondria and of acridine orange by lysosomes were strongly diminished, though not abolished. Cyclosporin may thus interfere at a step of activation prior or concurrent to those early changes of lymphocyte physiology. It looks like that it allows mitogen-activated cells to go through part of the mitochondrial maturation which precedes initiation of nuclear DNA synthesis, after which the cells remain blocked at that incomplete maturation level.