MODULATION OF IN-VITRO T-CELL ALLOREACTIVITY BY SYNTHETIC RETINOIDS

Diversity of the effects of retinoids on virtually all components of t he immune system makes them important immunomodulators. We recently su ggested the mechanism of the inhibitory effect of some synthetic retin oids on lectin-induced T cell proliferation, acting predominantly on e vents occurring after the interaction of IL-2 and its receptor. To ide ntify further immunomodulatory effects, two synthetic retinoids, etret inate and tretinoin, have been studied in a model of the in vitro prol iferative response of rat T lymphocytes to alloantigens. Both retinoid s, present at non-toxic concentrations, significantly decreased the ly mphocyte proliferation in the unidirectional mixed lymphocyte reaction . In experiments designed to examine whether decreased proliferative r esponse to alloantigens is a result of the reduced antigen presenting properties of stimulator cells caused by retinoids, it was shown that preincubation of allogeneic stimulator cells with either etretinate, o r tretinoin enhanced rather than reduced their capacity to stimulate f resh responder lymphocytes. Finally, examination of the effect of reti noids on the generation of non-specific suppressor T cells by Con A sh owed that tretinoin and etretinate potentiated the induction of cells which inhibit alloantigen-stimulated proliferation of fresh responder cells. Thus, our results strongly support the concept that, besides a direct inhibitory effect of synthetic retinoids on alloresponsive T ce lls, an additional indirect mechanism may exist, which involves potent iation of the induction of suppressor T cells.