Effect of phorbol esters on alloimmune cytolysis.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) profoundly affects cytolytic T-lymphocyte activity. Alloimmune C57BL/6 (H-2b anti-H-2d) cytolytic splenocytes treated with TPA, 0.3 to 3.0 ng/ml, killed specific P815 (H-2d) targets significantly better than did untreated controls as measured in 4-hr 51Cr release microcytotoxicity assay. Higher concentrations of TPA in the 30- to 100-ng/ml range significantly inhibited cytolytic function. The non-tumor-promoting analog, 4 alpha-phorbol-12,13-didecanoate, failed to affect killing at all doses tested. TPA-induced augmentation of cytolytic function requires an immunologically sensitized splenocyte population, since normal nonimmunized splenocytes treated with TPA did not kill target cells. Furthermore, treatment of splenocytes with anti-Thy 1,2 antibody and complement abrogated killing, indicating that T-lymphocytes mediate the killing. The TPA-induced effect does not require macrophage-like cells, since augmented killing occurred despite the removal of glass-adherent or iron-phagocytosing cells. Finally, the cytolytically augmented effector cells remain immunologically specific, since the nonspecific targets, syngeneic EL4 (H-2b) and third-party L929 (H-2k), are not killed. Thus, low levels of TPA augment the cytolytic ability of alloimmune T-lymphocytes against their specific target cells.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008223:Lymphoma / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology; D010704:Phorbols / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate