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Characteristics of Disparate Histocompatibility Barriers in Congenic Strains of Mice

II. Antibody-Associated Suppression¹

Department of Medical Microbiology and Immunology, University of California, Los Angeles 90024

Abstract

Characteristics of specific immunologic suppression were investigated in C57BL/10 congenic mouse strain combinations disparate at non-H-2 loci as a function of strong, moderate, and weak incompatibilities. These immunogenetic barriers were defined by both graft-vs-host reactivity and distinctive skin allograft survival times. Intraperitoneal injection of neonates with varying doses (2 x 10⁶ to 20 x 10⁶) of allogeneic spleen cells led to degrees of subsequent donor skin allograft acceptance which were closely dependent upon the interallelic combination. However, long-term skin allograft acceptors consistently produced serum alloantibodies against donor cells detectable in vitro by both cytotoxicity and hemagglutination-migration assays. The effectiveness of this specific antibody-associated suppression of transplantation immunity suggestive of enhancement was inversely proportional to the strength of the immunogenetic barrier and directly proportional to donor cell dosage. Increased immunogenetic incompatibility required increased dosage of allogeneic cells to induce specific suppression. The weaker the incompatibility the higher the incidence of effective allogeneic suppression and of concomitant alloantibody production obtained at lower antigen dosage. Coexistence of suppression of transplantation immunity (thymus-derived cell pathway blocked) with continuing anti-donor alloantibody production (bone marrow-derived cell pathway open) was found to be characteristic of the allograft-tolerant state.

Footnotes

¹ This work was supported by Public Health Service research Grant AI 07970 from the National Institute of Allergy and Infectious Diseases.

² Supported by Public Health Service Training Grant 5T01-AI-00249 from the National Institute of Allergy and Infectious Diseases.

³ Present address: The Jackson Laboratory, Bar Harbor, Maine 04609.