Potentiation of mitogen-induced human T-lymphocyte activation by retinoic acid

The capacity of retinoic acid to modulate human T-lymphocyte and B-lymphocyte activation by mitogens was examined. T-lymphocyte proliferation stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) or phytohemagglutinin was enhanced by 5 nM to 5 microM retinoic acid in a dose-dependent manner with a 65 +/- 35% (SD) increase (n = 6, P less than 0.01) in TPA-stimulated proliferation induced by 5 microM retinoic acid. Retinoic acid enhanced T-lymphocyte proliferation over a wide range of background proliferation induced by different TPA concentrations. Retinoic acid alone did not stimulate T-lymphocyte proliferation. In contrast retinoic acid inhibited B-lymphocyte proliferation stimulated by TPA or phytohemagglutinin with 26.7 +/- 23.4% inhibition of TPA-stimulated proliferation induced by 5 microM retinoic acid (P less than 0.02). Retinoic acid had intermediate effects on the proliferation of different mixtures of T- and B-lymphocytes stimulated by TPA or phytohemagglutinin. The recognition that retinoic acid has opposing effects on human T- and B-lymphocyte activation by mitogens may account for the conflicting reports of the effects of retinoids on the immune response of unpurified human lymphocyte preparations.