Acceptance of Allogeneic Tumor and Skin Grafts in Backcross Progeny of a Homograft-Tolerant Male

Abstract

Breeding of a C3H male tolerant to strain A tissue with (A × C3H)F₁ hybrid females produced a backcross population which almost uniformly accepted a spontaneous (A × C3H)F₁ hybrid mammary adenocarcinoma. These progeny also accepted an eighteenth transplant generation strain A mammary adenocarcinoma in higher incidence than would be expected in a normal backcross population where susceptibility is determined by a set of multiple, dominant histocompatibility genes. The alteration in the normal expression of histocompatibility observed in these backcross progeny of the tolerant animal suggests a change induced by the presence of strain A cells during the maturation of C3H germ plasm. Backcross animals produced at a later date by the tolerant animal bred with the (A × C3H)F₁ hybrid females showed a significant number of animals accepting (A × C3H)F₁ hybrid skin grafts compared with the tolerant backcross controls given or not given injections. When the tolerant backcross progeny were regrafted with strain A skin, these allogeneic grafts were also accepted. Finally, a group of the backcross progeny tolerant to (A × C3H)F₁ tissue, when regrafted with (C57BL/1 × C3H)F₁ hybrid skin, showed prompt graft rejection indicating a degree of specificity in the observed change. It is suggested that the utilization of the breeding model of actively acquired tolerance with the backcross population may provide further information about the heritable effects of germ-plasm exposure to cells of a foreign genotype.