Graft-versus-host disease in rats after donor treatment with cyclophosphamide and spleen cells of host origin.

Lethally irradiated Lewis-Brown Norway F1 hybrid (LBN) rats were grafted with either marrow or marrow and spleen cells from normal Lewis (L) donors. All recipients of inocula containing both marrow and spleen cells died of graft versus host (GVH) disease. In other irradiated and grafted rats, the severity of the GVH disease was reduced by challenge of the donor with LBN spleen cells prior to or after treatment with cyclophosphamide (CY). The magnitude of this suppressed immunity depended on the interval between the administration of CY and the ailogeneic spleen cells. Maximum suppression was obtained when donors received CY on day 0 and LBN cells on day +1. In all experiments, the treated donors were sacrificed on day +7. The observed immunosuppression was shown to result from the synergistic action of CY and cells bearing the alloantigens of the recipient. Furthermore, the phenomenon was demonstrated to be antigen specific.