Effects of retinoids on human thymus-dependent and thymus-independent mitogenesis

The effects of all-trans-retinoic acid (RA), 13-cis-retinoic acid, and N-(4-hydroxyphenyl)retinamide on the mitogenic responses of various populations of human lymphocytes have been evaluated. Superoptimal concentrations of mitogens allowed the greatest RA-induced potentiation of lymphocyte proliferation. All three retinoids at concentrations as low as 5 x 10(-14)M significantly potentiated the proliferation of adenoidal and tonsillar lymphocytes stimulated by pokeweed mitogen (PWM). However, the responses of adenoidal and tonsillar lymphocytes to Staphylococcus aureus Cowan strain A were not potentiated by retinoids. Retinoids also caused significant potentiation of proliferation of PWM-stimulated peripheral blood lymphocytes (PBL). However, endpoint concentrations of retinoids required to significantly potentiate PBL proliferative responses to PWM were much higher than required for potentiation of adenoidal or tonsillar lymphocytes. PBL responses to concanavalin A (Con A) were significantly potentiated by retinoid concentrations as low as 10(-8) to 10(-10) M. Retinoid-potentiated responses were also observed wi Con A-stimulated thymocytes, but the endpoint concentrations required for significant potentiation were 10-fold higher than required to potentiate PBL responses to Con A. These data indicate that the sensitivity of lymphocytes to the retinoid-mediated potentiation of mitogenesis depends on the lymphoid compartment from which the cells are obtained. Tonsillar and adenoidal lymphocytes were the most responsive of the lymphocytes tested to the retinoid-induced potentiation of PWM responses. In addition, retinoids appear to selectively potentiate T cell-dependent proliferative activity.