Effects of two bisdioxopiperazines on mouse B-and T-cell function.

Abstract

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.

• Authors: G Dennert, L E Hatlen, D F Tucker
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 54 Issue 3 Pg. 621-9 (Mar 1975) ISSN: 0027-8874 [Print] United States
• PMID: 804564 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antilymphocyte Serum
• Immunosuppressive Agents
• Piperazines
• Razoxane
• Cyclophosphamide

Topics

• Animals
• Antibody Formation (drug effects)
• Antigen-Antibody Reactions (drug effects)
• Antilymphocyte Serum (pharmacology)
• B-Lymphocytes (drug effects)
• Cyclophosphamide (pharmacology)
• Cytotoxicity Tests, Immunologic
• Erythrocytes (immunology)
• Female
• Hemolytic Plaque Technique
• Immunity, Cellular (drug effects)
• Immunosuppressive Agents
• Mast-Cell Sarcoma (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Neoplasm Transplantation
• Piperazines (pharmacology)
• Razoxane (pharmacology)
• Spleen (immunology)
• T-Lymphocytes (drug effects)
• Thymus Gland (immunology)