[Study of immunosuppressive mechanism of deoxymethylspergualin in vitro]

Mechanism of action of Deoxyspergualin (DSG) in vitro has not been clarified, because it is unstable in solution. I studied its mechanism in vitro using Deoxymethylspergulin (MeDSG) that is stable in solution. Action of MeDSG was studied using human lymphocyte and a human T cell clone which was established in our laboratory. MeDSG showed dose dependent inhibition of blastogenesis in MLR. MeDSG inhibited the response by about 50% at the concentration of 10 micrograms/ml. It is a very interesting point that MeDSG added at 3 days later suppressed MLR. But MeDSG did not suppress MLR added at 4 days later or 2nd MLR. MeDSG did not have effects on the production of IL-1, IL-2 and the expression of IL-2 receptor on stimulated lymphocyte by mitogen. But MeDSG suppressed IFN-gamma production induced stimulation of alloantigen at only concentration of 1 microgram/ml. MeDSG did not suppress proliferation of helper T cell clone. On the other hand, CsA suppressed IL-2 receptor expression and proliferation of helper T cell clone. These results showed MeDSG act on relatively late phase of immunoreaction. From in vitro results, when we use DSG for clinical acute rejection, it is more appropriate to use DSG and Methylprednisolone at the same time to get early recovery.