Determination of the suppression of the cellular immune response of mice with donor-specific gamma globulin during chimeric state

• Published in: Progress in clinical and biological research Vol. 161; p. 77
• Main Author: Kende, M
• Format: Journal Article
• Language: English
• Published: United States 1984
• Subjects: Animals; Chimera; gamma-Globulins - immunology; Immunity, Cellular - drug effects; Immunoglobulin Allotypes; Immunosuppression; Immunosuppressive Agents - pharmacology; Male; Mice; Mice, Inbred Strains; Skin Transplantation; Transplantation, Homologous
• ISSN: 0361-7742

With the exception of purine and pyrimidine antagonists the immunosuppressive properties of compounds can be monitored with the donor-specific gamma globulin allotype method. Lympholytic drugs such as alkylating agents are particularly active during the preinduction interval (before injection of the antigen) of the immune response. Antimetabolites and analogs such as 6-mercaptopurine and methotrexate are most active over the induction period (at the time and immediately after the antigen administration) which can explain why these strongly immunosuppressive compounds were inactive in this assay system. However, modification of the assay could render it suitable to monitor the immunosuppressive activity of compounds of this class. All but one of the 22 compounds were administered 4-6 hours before the lymphoid cell grafting and during that interval not all of the drugs may have been cleared from the body. Therefore, residual drug activity could have wholly or partially destroy the grafted cells resulting in a false negative allotype titer. Administration of the lymphoid cells 24 hrs after the drug, as in the case of BIC, could yield immunosuppression. Very good correlation exists between allotyping and skin grafting. This correlation allowed the designation of low allotype titers (1:2 and 1:4) as markers of weak immunosuppression. A host in a weak immunosuppressed state is still able to mount sufficient response against skin grafts and probably against other types of immune response manifestations. This assay system is also suitable to simultaneously measure the humoral immune response for a prolonged period (upon injection of the eliciting antigen such as SRBC) without the need to sacrifice the host. Furthermore, reestablishment of the T and B lymphocyte mediation of cellular and humoral immune responses respectively, can be sequentially monitored in the same host, a feature which is not shared by in vivo/in vitro procedures such as assay for delayed hypersensitivity, graft versus host reaction and cytotoxic reactivity to virus-infected cells. These methods are being employed to assess the inadvertent modification of the immune response by food, drugs, chemicals, and environmental containments (Dean, Padarathsingh, Jerrells 1979 Sprefico 1980 Ghaffar, Paul, Lichter, Wellham Sigel 1980 Dean, Luster, Boorman, Padarathsingh, Luebke Clements 1980). Because of the heterogeneity of gamma globulin in animal species, the donor-specific allotyping can be applied to the majority of the food and companion animals of veterinary interests with all the above discussed advantages.