Distinct effects of phorbol esters and exogenous diacylglycerols in the induction of murine thymocyte proliferation.

Murine thymocytes were stimulated with the protein kinase C activating agents Phorbol-12-myristate-13-acetate (PMA) or a more physiological membrane permeant diacylglycerol (dioctanoyl-sn-glycerol, DiC8) in the presence or absence of exogenous lymphokines (rIL-1 beta, rIL-2). Whereas PMA directly induced reactivity to rIL-2, DiC8 did not but had to synergize with the calcium ionophore Ionomycin. Expression of the p55 chain of the IL-2 receptor behaved similarly. In the absence of exogenous rIL-2, thymocytes proliferated in response to a combination of Ionomycin and PMA; however, replacing PMA by a single addition of DiC8 did not result in proliferation. Stimulation with Ionomycin plus repeated addition of DiC8 induced a low level of thymocyte proliferation and further addition of rIL-1 beta resulted in a significant increase. Purified immature (L3T4-Lyt2-) thymocytes behaved similarly, but showed an increased sensitivity to rIL-1 beta. Taken together, the data support the idea that PMA and the more physiological diacylglycerols do not possess totally equivalent activities in lymphocyte stimulation.