Genetic requirements for the development of the GVH reaction following small-bowel transplantation.

The genetic requirements for the development of graft-versus-host (GVH) disease have been investigated in a model of semiallogenic, heterotopic small-bowel transplantation in the rat. Following semiallogenic MHC-incompatible small-bowel transplantation, all graft recipients showed characteristic signs of GVH disease and died within 14 days. On autopsy the transplanted bowel was normal, while the recipient's bowel was dilated and distended with gas. Histology showed a generalized cell infiltration of the connective tissue with macrophages and lymphocytes. After semiallogenic, RT1.A-incompatible, small-bowel transplantation, the graft recipients developed mild and temporary symptoms of GVH disease between days 25 and 40. Only two of the six animals died, while the remaining animals survived the observation period. Small-bowel transplantation across an isolated RT1.C barrier was unable to induce GVH reaction. These results indicate that the development of GVH disease after small-bowel transplantation is controlled genetically by the MHC. Class II MHC incompatibility is necessary for the induction of an acute and lethal GVH reaction.