Phorbol myristate acetate and in vitro T lymphocyte function. II. Influence of PMA and supernatants from PMA-treated P388D1 cells on the proliferation of cloned T cells.

Neither the culture supernatants from P388D1 cells pulsed with phorbol myristate acetate (PMA), nor PMA itself in concentrations ranging from 10(-6) M to 10(-9) M, are directly mitogenic for murine T lymphocyte clones, yet both markedly augment the antigen-driven proliferation of many, but not all, cloned T lymphocytes. The component of PMA-induced P388D1 supernatant responsible for its co-mitogenic activity is probably PMA, rather than interleukin 1. For responsive clones, the co-mitogenic effect of PMA requires stimulator cells that display the specific allogeneic determinants recognized by the clones. This response persists after T cells are removed from the stimulating population, ruling out induction of mitogenic lymphokines from stimulator T cells by PMA as a primary mechanism for augmentation of clonal proliferation. Both splenocytes and thymocytes cooperate with PMA for enhanced clonal expansion, but heat treatment (45 degrees C, 45 min) of thymocytes destroys their cooperative capacity. PMA can also potentiate the lymphokine-driven proliferation of cloned T cells, indicating that PMA can, under certain conditions, influence T cell clonal expansion by a direct action on T lymphocytes.