Modulation of in vitro T cell alloreactivity by synthetic retinoids.

Diversity of the effects of retinoids on virtually all components of the immune system makes them important immunomodulators. We recently suggested the mechanism of the inhibitory effect of some synthetic retinoids on lectin-induced T cell proliferation, acting predominantly on events occurring after the interaction of IL-2 and its receptor. To identify further immunomodulatory effects, two synthetic retinoids, etretinate and tretinoin, have been studied in a model of the in vitro proliferative response of rat T lymphocytes to alloantigens. Both retinoids, present at non-toxic concentrations, significantly decreased the lymphocyte proliferation in the unidirectional mixed lymphocyte reaction. In experiments designed to examine whether decreased proliferative response 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, or tretinoin enhanced rather than reduced their capacity to stimulate fresh responder lymphocytes. Finally, examination of the effect of retinoids on the generation of non-specific suppressor T cells by Con A showed 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 cells, an additional indirect mechanism may exist, which involves potentiation of the induction of suppressor T cells.