Effects of two bisdioxopiperazines on mouse B-and T-cell function.
The immunosuppresive effects of the bisdioxopiperazines ICRF 154 and ICRF 159 on the function of bone marrow-derived lymphocytes (B cells) and thymusderived lymphocytes (T cells) were assessed and compared with those of cyclophosphamide (CPA). Mice given foreign erythrocytes with any of these drugs for 3 or 5 days showed suppressed antibody responses due to the inhibition of thymus-derived cooperating lymphocyte (T-helper cell) priming and inactivation of B cells in the spleen. In contrast, 3 days of drug treatment after the injection of allogeneic tumor cells only partially inhibited T cell-dependent cytotoxicity. Moreover, when irradiated tumor cells were given for 3 days with CPA or ICRF 154, enhancement rather than inhibition of cytotoxicity was the usual response. However, with both types of immunization, no thymus-derived cytotoxic lymphocytes (T killer cells) could be generated after prolonged treatment (6 daily injections) with any of the 3 drugs. Administration of drugs before antigen also resulted in selective drug action, i.e., a relative increase in the proportion of thy-1-positive cells in the spleen. After challenge in vivo or in vitro with erythrocyte antigens, the plaque-forming cell responses of these spleens were raised up to twofold, probably because they had higher T-helper cell activity than untreated controls. Similar pretreatment before immunization with allogeneic tumor cells also led to enhanced T-killer cell activity, but only in ICRF 154- and CPA-treated mice. These observations suggest that under certain conditions, the bisdioxopiperazines and CPA have selective effects on B-cell rather than T-cell function.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D000961:Antilymphocyte Serum / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006462:Hemolytic Plaque Technique; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology*; D011929:Razoxane / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000276:immunology
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D010879:Piperazines; D011929:Razoxane; D003520:Cyclophosphamide