Prevention and treatment of graft-versus-host disease by down-regulation of anti-host reactivity with veto cells of host origin

Abstract

Control of graft-versus-host disease (GVHD) post allogeneic spleen cell transplantation was partly achieved by administration of host-type lymphocytes. (C57BL/6 × BALB/c) F1 mice were conditioned by total body irradiation and transplanted with parental C57BL/6 spleen cells to induce severe GVHD. Infusion of mature host-type lymphocytes did not change the degree of chimerism but protected most of the recipients from lethal GVHD. Treatment of host-type blood cells with anti-CD8 antibodies resulted in loss of the GVHD protective effects mediated by host cells, whereas after treatment of the host with anti-CD4 antibodies protective host cells given 4 days after induction of GVHD resulted in successful rescue of all transplanted recipients from lethal GVHD. Administration of host blood cells could effectively protect against GVHD induced by donor spleen cells and low-dose rIL-2. GVHD protection resulted from down-regulation of alloreactive donor T cells and not by rejection of GVHD effector cells. Taken together, administration of host hematopoietic cells particularly host CD8⁺ T cells, may be considered for prevention or control of GVHD following allogeneic bone marrow transplantation, thus also explaining the increased resistance of mixed chimeras to GVHD.