Modulation of cell-mediated alloimmunity by BCG. I. Antagonism and potentiation of immunosuppression caused by cytarabine.
The ability of iv administered BCG to antagonize immunosuppression caused by injection of the antimetabolite cytarabine (beta-cytosine arabinoside; ara-C) was investigated in C57BL/6 mice. Treatment with BCG 10 days before alloimmunization with killed L1210 tumor cells decreased spleen T-cell-mediated cytolysis against allogeneic P815Y tumor cells, as measured by a short-term 51Cr release assay, and potentiated immunosuppression due to ara-C. In contrast, spleen cell-mediated immunity (CMI) that was assayed by a 48-hour microcytotoxicity assay (MCA) was augmented by systemic BCG administered before alloimmunization. Pretreatment with BCG resulted in a complete and long-lasting protection against the immunosuppressive effects of ara-C on this CMI as measured by the MCA. Treatment with BCG after cytoreductive therapy resulted in a significant, although transient, reversal of immunosuppression. Depending on the type of response and thus the type of effector cell measured, BCG acts as a moderate immunosuppressive agent or a strong immunopotentiator of CMI.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001500:BCG Vaccine / Q000494:pharmacology*; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007165:Immunosuppression Therapy; D007939:Leukemia L1210 / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D003561:Cytarabine