INHIBITION OF THE GRAFT-VERSUS-HOST REACTION BY PRETREATMENT OF DONORS WITH VARIOUS ANTIGENS

Abstract

The effect of pretreating mice with diverse antigens on the capacity of their spleen cells to produce fatal graft-versus-host (GVH) disease across an H-2 histocompatibility barrier has been investigated. The mortality rate of midlethally irradiated recipients given spleen cells from untreated donors was a linear function of the number of cells transferred. Equal numbers of spleen cells from antigen-treated donors consistently showed a reduction in their capacity to produce fatal GVH disease. Microbial antigens were ordinarily more potent than soluble protein antigens in producing this effect. Furthermore, intensive daily antigen pretreatment generally caused greater impairment of spleen cell GVH reactivity than pretreatment with lower doses of antigen. Relative dilution of GVH competent cells as a result of splenic hyperplasia in antigen-treated donors accounted for only a portion of the observed effect. The data indicate that when donor cells are actively engaged in processing nontransplantation antigens, there occurs a significant interference in their GVH reactivity.