Lymphocyte activation by OKT3: cyclosporine sensitivity and synergism with phorbol ester

Lymphocyte activation by the mitogenic monoclonal antibody OKT3 is less effective than activation by mitogenic lectins such as phytohaemagglutinin (PHA) and concanavalin A (Con A). Activation by OKT3 is also very sensitive to inhibition by cyclosporine (CSA), which selectively inhibits Ca2+-activated steps in the activation process. In addition, the magnitude of the OKT3 response can be raised to that seen with mitogenic lectins by coincubation with phorbol esters (which activate protein kinase C). These observations suggest that OKT3 may deliver efficiently the Ca2+ signal involved in the initiation of lymphocyte activation, and that the comparatively weak overall response is due to a failure to generate a second signal, probably the activation of protein kinase C, as efficiently as the mitogenic lectins.