Rapid loss of sensitivity of mitogen-induced lymphocyte activation to inhibition by cyclosporin A.
The ability of the immunosuppressive drug cyclosporin A (CS-A) to inhibit the activation of lymphocytes by phytohaemagglutinin (PHA) and concanavalin A (Con A) is progressively lost over the 8-hr period following mitogen addition. This process is dependent on the presence of Ca2+ in the culture medium and is complete at a time when activation still requires the continued presence of the mitogen. While inhibition by CS-A is reduced to some extent by lymphokines produced by mitogen-activated cultures, the initial loss of sensitivity to CS-A is too complete and too rapid to be accounted for in this way. We conclude that CS-A inhibits an early Ca2+-dependent step in mitogen-induced activation that is not in itself sufficient to commit the cells to initiate proliferation, but is required for later steps in the activation process, including lymphokine production.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003470:Culture Media; D003524:Cyclosporins / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013552:Swine
D003470:Culture Media; D003524:Cyclosporins; D008222:Lymphokines; D010835:Phytohemagglutinins; D003208:Concanavalin A; D002118:Calcium