Effects of Immunosuppressants and Cytostatics

Beginning in 1967, our laboratory has published a number of investigations of the nonsyngeneic stem ceil-inactivation phenomenon (1-3). I t has been shown that, after transplantation of a mixture of allogeneic lymphoid and hemopoietic cells into lethally irradiated hosts, stem elements of the mixture are inactivated by allogenic lymphocytes of the graft. In other words, after transplantation of such a cell mixture exogenous colony-forming units (CFU) ~ give no colonies in recipient spleens. On the basis of this fact we supposed that lymphoid cells of parental genot)~pe, being transplanted into sublethally irradiated F1 recipients, must inactivate host endogenous CFU, i.e., inhibit endogenous colony formation. The degree of inhibition may serve as a quantitatively accurate value for graft-versus-host (GVH) reaction. I t is evident that such an experimental system is characterized by the development of two simultaneously occurring processes: multiplication of endogenous CFU and homograft reaction against them by transplanted lymphocytes. Both processes may be quanti tat ively estimated by counting the number of spleen colonies in animals of corresponding experimental groups. By this technique, it is possible to compare quantitatively two of the most important actions of immunosuppressive agents: their mitostatic effect (CFU inhibition), and their lymphotoxic action; the latter is a true immunosuppressive effect, the abolition of endogenous CFU inactivation.