Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD8 T-lymphocytes.
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.
Slater
L M
LM
Department of Medicine, University of California at Irvine 92717, USA.
Sweet
P
P
Stupecky
M
M
Reynolds
J T
JT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic; D005047:Etoposide / Q000008:administration & dosage*; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007939:Leukemia L1210 / Q000188:drug therapy / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D005047:Etoposide; D016572:Cyclosporine