title: Antilymphocytic antibodies and marrow transplantation. VIII. Recipient conditioning with Clq-affine monoclonal anti-pan T antibodies prevents GVHD in homozygous fully mismatched mice.
abstract: An approach to suppressing secondary disease with antibodies was studied that differed from conventional antibody treatment of donor marrow in vitro. It consisted of the selection of anti-Thy-1 antibodies with high affinity for Clq, the first subunit of the complement cascade, and a single injection of such antibodies into prospective irradiated marrow recipients. Monoclonal mouse IgM and rat IgG 2c antibodies of high titers in complement-dependent test systems but with low affinity for Clq caused little immunosuppression. Monoclonal rat IgG2b or mouse IgG2a anti-Thy-1 antibodies with high affinity for Clq prevented acute and chronic mortality of graft-v-host disease (GVHD), however, when injected in irradiated CBA or AKR mice prior to C57BL/6 spleen and/or bone marrow cell transfusion. This treatment simultaneously suppressed residual host-v-graft reactivity of the irradiated mice, so that permanent hematopoietic engraftment ensued even at 5 or 6 Gy. Full chimerism and specific tolerance were obtained. Primary immune response to SRBC was clearly depressed in the chimeras; secondary immune response was not. Clearance of T cell antibody activity (greater than 6 days), timing, and dose of injected antibody, as well as other modalities of the conditioning treatment that may have contributed to the remarkable immunosuppression, are discussed.
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000954:Antigens, Surface / Q000276:immunology*; D016026:Bone Marrow Transplantation; D003166:Complement Activating Enzymes / Q000276:immunology*; D015922:Complement C1q; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007132:Immunoglobulin Isotypes; D007518:Isoantibodies; D018800:Thy-1 Antigens; D015922:Complement C1q; D003166:Complement Activating Enzymes