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, heteroto pic small-bowel transplantation in the rat. Following semiallogenic MH C-incompatible small-bowel transplantation, all graft recipients showe d characteristic signs of GVH disease and died within 14 days. On auto psy the transplanted bowel was normal, while the recipient's bowel was dilated and distended with gas. Histology showed a generalized cell i nfiltration 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 dis ease between days 25 and 40. Only two of the six animals died, while t he remaining animals survived the observation period. Small-bowel tran splantation across an isolated RT1.C barrier was unable to induce GVH reaction. These results indicate that the development of GVH disease a fter small-bowel transplantation is controlled genetically by the MHC. Class II MHC incompatibility is necessary for the induction of an acu te and lethal GVH reaction.