The effect of deoxyspergualin (DSG, NKT-01) on humoral immunity was investigated both in vitro and in vivo. DSGinhibited the primary and secondary responses to T cell-dependent antigens and the response to T cell-independent antigens in thymic and athymic mice. However, natural antibodies in non-sensitized mice were affected less by the administration ofDSG. The agent produced a dose-dependent inhibition of B cell proliferation and antibody production to lipopolysaccharide in vitro. Suppression of secondary antibody response was also shown, whenever antigen stimulation was not given, antibody production was not affected. These results suggest that DSGaffects the proliferative stage ofB lymphocytes in such a way as to inhibit their growth and antibody production.
Deoxyspergualin has strong immunosuppressive activity in animals. However, it shows less in vitro immunosuppressive activity at the therapeutic concentration used for in vivo administration. Recently, we reported that there are sometechnical problems with in vitro experiments. In this report, the effects of spergualins were examined under in vitro conditions which excluded these problems, and compared with cyclosporine A (CYA). Spergualins have suppressive effects on mixed lymphocyte response (MLR)and cytotoxic T lymphocyte induction. Furthermore, interleukin-2 (IL-2) induced proliferation of concanavalin A blasts and CTLL-2were inhibited at low concentration. However, spergualins have little effect in the early stage of MLR or the mitogenresponse. These results suggest that spergualins act on the proliferation and differentiation of T cells which respond to growth factors, such as IL-2.
Deoxyspergualin(DSG, NKT-01), an analog of spergualin15, has antitumor activity2) and immunosuppressive activity35. As reported previously, DSG acts to prolong allogeneic4~8) and xenogeneic graft9) survival in various experimental transplantation models and shows therapeutic effect on various autoimmune disease models10). Wehave been investigating the mode of action of DSGon immunosuppressive activity, but it shows little in vitro activity at the therapeutic concentration used for in vivo administration. Recently we reported that there are some technical problems with in vitro experiments, that is, stability of DSGin culture medium115 and oxidation by amine oxidase in fetal calf serum (FCS)12). In this report, the in vitro effect of spergualins was examined using a stable analogue, deoxymethylspergualin (MeDSG), and a culture mediumwhich has practically no amine oxidase activity. The immunosuppressive effect of spergualins on murine lymphocytes were demonstrated in vitro and the immunosuppressive properties were compared with cyclosporine A (CYA).
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