In vivo immunosuppression by pan-T cell antibodies relates to their isotype and to their C1q uptake.
There is considerable interest in the use of monoclonal anti-T cell antibodies for immunosuppression during organ transplantation. However, the in vitro cytotoxic titers of these monoclonal reagents do not correlate with their immunosuppressive potency when injected in vivo. A relationship nevertheless seems to exist between immunosuppression and the isotype of anti-mouse Thy-1 antibodies, because among several anti-Thy-1 antibodies of mouse and rat origin, the only two found to cause immunosuppression in vivo belonged to the rat IgG2b and mouse IgG2a isotype. We show here that a quantitative positive correlation exists between an antibody-induced humoral effector mechanism and immunosuppression. We measured the uptake of the C1q complement subunit by polyclonal rabbit and rat anti-thymocyte globulin and also seven monoclonal anti-Thy-1 antibodies in an immunohistochemical assay or a radioimmunoassay. Immunosuppression was studied in a murine graft-vs-host and skin allograft model. Our results suggest strongly that a stable association between the C1 protein and a potential binding antibody is an essential prerequisite of antibody-dependent cell inhibition in vivo that suppresses the immunoresponse against strongly incompatible transplantation antigens.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D000961:Antilymphocyte Serum; D003166:Complement Activating Enzymes / Q000276:immunology* / Q000378:metabolism; D003172:Complement C1 / Q000276:immunology* / Q000378:metabolism; D015922:Complement C1q; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000961:Antilymphocyte Serum; D003172:Complement C1; D007074:Immunoglobulin G; D018800:Thy-1 Antigens; D015922:Complement C1q; D003166:Complement Activating Enzymes