Regulation of allospecific suppressive cell generation in vitro.

Control of the generation of suppressive cells (SC) in allogeneic mixed lymphocyte cultures (MLC) has been re-investigated. Cells taken from 3-6 days old ("early", e-MLC) suppressed lymphocyte proliferative responses when transferred to a second MLC. Suppression was not allospecific, nor restricted to the autologous responder. In contrast, cells from MLC 7-10 days old ("late", l-MLC) mediated weak but specific suppressive activity, which was HLA-restricted. Addition of early MLC cells (e-MLC1) to a second MLC (MLC2), blocked the further generation of non-specific suppressive activity in that MLC, suggesting the presence of downregulatory components for SC generation. Nonetheless, the generation of allospecific suppression in late MLC2 (l-MLC2) was enhanced rather than inhibited under these conditions. In separate experiments, a T cell clone (TCC) was isolated which mimicked the action of e-MLC cells on SC generation, namely, down-regulation of non-specific but amplification of specific SC generation. This clone carried the "alternative" tau/delta T cell receptor. Thus, tau/delta+ "antisuppressor" regulatory cells may have a role in the establishment and maintenance of allograft tolerance.