CHARACTERISTICS OF DISPARATE HISTOCOMPATIBILITY BARRIERS IN CONGENIC STRAINS OF MICE

Abstract

SUMMARY The nature and components of “antigenic strength.” were investigated in C57BL/10 congenic strain combinations disparate at non-H-2 loci and selected for strong, moderate, and weak incompatibilities based on skin allograft survival times. Graft-versus-host reactions (GVHR) were studied following injection of varying doses (1 X 106-40 X 106) of normal or preimmunized adult spleen cells into newborn mice. The distinctive strengths of non-H-2 immunogenetic barriers were consistent and parallel as measured by GVHR and skin allograft survival times. The interallelic combination rather than the H locus as such determined the intensity of the histoincompatibility. Decreasing immunogenetic incompatibility was correlated with increasing dosage of spleen cells required to evoke allogeneic disease. The stronger the immunogenetic barrier, by contrast, the greater the efficacy of small doses of immunocompetent cells in producing measurable GVH disease. The weaker the histoincompatibility, the later the time of onset of GVHR and the greater the interval between onset and death. Profound splenic and thymic atrophy coupled with peripheral lymphopenia were the central features of terminal allogeneic disease in non-H-2 disparate mice. GVHR intensified by preimmunized donor spleen cells led to increased deaths and decreased median survival times. The weaker the histocompatibility barrier, the greater was the potential efficacy of preimmunization of evoking GVHR; the longer time required to achieve maximum effectiveness of donor cell preimmunization, the weaker the immunogenetic barrier.