In vitro kinetic study of the immunosuppressive effect of deoxymethylspergualin on human peripheral blood mononuclear cells.

The immunosuppressive mechanism of Deoxymethylspergualin (MeDSG) was investigated in human subjects by in vitro assay. In an allogeneic mixed lymphocyte reaction (MLR), MeDSG was added at different times. A moderate immunosuppressive activity against allogeneic blastogenesis was seen even when MeDSG was added on the 4th day from the initiation of culture. In the cell-mediated lymphocytolysis (CML) assay, MeDSG was added to bulk MLR in CML in the same manner. For the strong suppression of CML, however, MeDSG should be added to bulk MLR within 2 days from the initiation of culture. There was a difference in immunosuppressive kinetic pattern of MLR and CML induced by MeDSG. In the study of the effect of MeDSG on the interleukin-2 (IL-2) production of allogeneic blast cells, MeDSG showed only a slight suppression. In the MeDSG induced regulator cell assay, these cells induced no suppression of fresh CML, even when they were adoptively transferred to fresh bulk MLR in CML at different times. In the subset analysis of surface phenotypes of allogeneic blast cells in MLR, IL-2R+ cells and CD8+ LFA1+ cells treated with MeDSG, were significantly decreased. These results indicate that MeDSG acts on a comparatively early stage of the afferent phase in allogeneic stimulation and suppresses development of cytotoxic lymphocytes strongly, without inhibition of IL-2 production or suppressive regulator cell induction.