Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD8 T-lymphocytes

Abstract

The role of the immune response in the chemotherapeutic cure of an intact host with neoplasia is not well defined. We have previously shown that the addition of cyclosporin A to VP-16 therapy of BDF/1 mice with L1210 leukemia produces immunity to leukemia in long-surviving host animals. We now characterize this immunity as being tumor specific and related to the participation of CD8 T-lymphocytes. Splenocytes derived from L1210 leukemia immune mice are cytotoxic to L1210 cells after in vitro restimulation, compared to splenocytes harvested from nonimmune control mice. This cytotoxicity is lost by CD8 T-lymphocyte depletion and persists in Ia antigen blocking experiments. Cytotoxicity is selective for L1210 leukemia compared to P388 leukemia, an alternate Ia antigen expressing methylcholanthrine-induced acute lymphoid leukemia, and L1210 leukemia-immune mice remain susceptible to P388 leukemia in vivo demonstrating specificity of the immune response generated by cyclosporin A/VP-16 therapy.