Immunological aspects of retinoids in humans. I. Analysis of retinoic acid enhancement of thymocyte responses to PHA.

We previously reported that retinoic acid (RA) enhances the blastogenic responses of human thymocytes. In this study, we explored the mechanism(s) of this effect by determining the phenotype of cells that show augmented responses to PHA and by analyzing RA effects on regulatory events mediated by interleukin-2 (IL-2). Our results indicate that RA is required early in the PHA activation process and that thymocytes affected by RA treatment already express the "mature" T3 antigen but lack T6 and Fc mu receptors. In the presence of saturating concentrations of exogeneous IL-2, RA caused further enhancement of both unfractionated and T3+ thymocyte proliferation, but could not induce immature T3- cells to become PHA responsive. RA treatment of thymus cells did not affect IL-2 production nor IL-2-dependent T-cell blast growth. RA-induced enhancement appears to induce increased sensitivity of T3+T6-Fc mu- thymocytes to PHA activation, but does not alter either IL-2-dependent proliferation or the accessory cells involved in IL-2 production.