Chronic graft-versus-host disease in rats after syngeneic bone marrow transplantation

A disease similar to the chronic graft-versus-host disease (cGVHD) seen following transplantation of human bone marrow was observed after syngeneic and allogeneic bone marrow transplantation in rats. Bone marrow grafts were exchanged between donors and recipients that were syngeneic or genetically different for the RT2 erythrocyte antigen locus by the use of AUG/AUG.2B and PVG/PVG.2A congenic pair donor/recipient strain combinations. After an initial period of well-being (120-180 days posttransplantation), several AUG and AUG.2B recipients of syngeneic or RT2-mismatched bone marrow developed clinical signs compatible with cGVHD. The clinical signs of the disease included: erythema, diffuse alopecia, thickened skin folds, and conjunctivitis. Laboratory findings included peripheral blood eosinophilia and impaired in-vitro proliferative responses to third-party spleen cells in the mixed lymphocyte reaction. Histological examination of the tissues of a limited number of rats with cGVHD showed subepidermal mononuclear inflammation with atrophy of the epidermis and adnexa of the skin, as well as plasmacytic hyperplasia of the lymphoid tissues. None of the PVG or PVG.2A recipients of syngeneic or RT2-mismatched marrow developed cGVHD. The development of cGVHD in AUG.2B recipients of syngeneic marrow and the absence of the disease in reciprocal marrow grafts between the PVG/PVG.2A rat strains suggests that the development of the disease in the AUG and AUG.2B recipients of RT2-mismatched bone marrow is not due to the RT2 disparity, but may be due to an autologous immune reaction. Furthermore, the finding that the cGVHD is only observed when the AUG and AUG.2B strains are used as recipients--not when the PVG or PVG.2A strains are used as recipients--suggests that the development of the disease is associated with the genetic background of the host and is independent of the background of the donor. It is possible that the use of high-dose cyclophosphamide treatment is involved in the pathogenesis of cGVHD, because the disease is observed only when the recipients are conditioned for transplantation with this immunosuppressive agent.