Deoxyspergualin, a novel immunosuppressant, markedly inhibits human mixed lymphocyte reaction and cytotoxic T-lymphocyte activity in vitro.

Abstract Deoxyspergualin (DSG) has demonstrated potent immunosuppressive activities in vivo . However, because of its lability in culture medium, the mechanism of activity has not yet been identified in vitro . In this study, a more stable analogue, deoxymethylspergualin (MeDSG), was used to investigate the in vitro immunosuppressive activity of DSG. MeDSG suppressed both human mixed lymphocyte reaction (MLR) and cytotoxi T-lymphocyte (CTL) activity at doses greater than 0.1 μg/ml in vitro . In kinetics studies, MeDSG was found to suppress a MLR when added on day 3 of a 7 day MLR incubation but cyclosporin A (CYA) suppressed a MLR only when added during the initial stage of a MLR (i.e. on day 1). In studies of cell surface phenotype in the MLR, MeDSG treatment decreased the numbers of CD8 + lymphocytes but those of CD4 + lymphocytes were not affected. In addition, MeDSG had no significant effect on interleukin-2 (IL-2) receptor expression or IL-2 production. These results suggest that MeDSG suppresses the T-cells which are proliferating competent cells such as cytotoxic T-cells (CD8 + ), but has a different mode of immunosuppressive action compared with CYA.