Mechanism of Calcium Ionophore and Phorbol Ester‐Induced T‐cell Activation

Abstract

We examined (he role of monocytes in T‐cell activation induced by phorbol myristate acetate (PMA) and calcium ionophore ionomycin. Depletion of monocytes from peripheral blood mononuclear cells (PBMC) was associated with the loss of inlerleukin‐2 (IL‐2) production, IL‐2 receptor (1L‐2 RI expression and proliferation, in response to cither PMA or ionomycin. Addition of monocytes to highly purified T cells resulted in the complete R‐constitution of IL‐2 production. 1L‐2R expression and proliferation by PMA‐stimulated lymphocytes. Exogenous IL‐2, but not interleukin‐l (IL‐l), could reconstitute the T‐cell responsiveness. Addition of monocytes to highly purified T cells stimulated with ionomycin resulted in partial reconstitution of IL‐2 production. II,‐2R expression and proliferation. Similarly, (he addition of exogenous lL‐2 to ionomycin‐stimulated T cells only partially reconstituted the response compared with PBMC, These results suggest that monocyte‐T‐cell interactions contribute to IL‐2 production and IL‐2R expression and are crucial events for PMA‐induced T‐cell proliferation. With ionomycin, monocytes play a role, in part, in inducing IL‐2 production, IL‐2R expression and proliferation. However, IL‐2 is not a sufficient signal to induce T‐cell proliferative response lo ionomycin, suggesting that an IL‐2‐independent mechanism may exist in ionomycin‐induced T‐cell proliferation.