Augmentation of mixed lymphocyte response. Stimulatory activity by phorbol ester

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a variety of phenotypic changes on normal and malignant cells. In chronic and acute lymphocytic leukemia we have observed a marked augmentation in mixed lymphocyte reaction stimulatory capacity (MLRs) following pretreatment of leukemia blasts with TPA. We have now characterized the effects of TPA on MLRs utilizing the non-T, non-B lymphoblastic leukemia-cell line, HOON. Following pretreatment with TPA (optimal concentration, 1.6 X 10(-10) M), but not with other phorbol esters, there was a marked increase in MLRs, particularly at lower stimulator-cell concentrations. This effect was maximal following a 44-hr preincubation period and the enhancement in MLRs was not accompanied by changes in levels of Ia expression. This cell line provides a model for determining the molecular basis for the TPA-induced augmentation of stimulatory capacity in the mixed lymphocyte reaction.