ANALYSIS OF REJECTION MECHANISM IN THE RAT TO MOUSE CARDIAC XENOTRANSPLANTATION - ROLE AND CHARACTERISTICS OF ANTIENDOTHELIAL CELL ANTIBODIES

Recent reports have demonstrated that humoral factors, especially anti bodies elicited by xenoantigens, play an important role in the rejecti on of concordant cardiac xenografts. These induced antibodies, however , have not been well characterized. Therefore, we investigated the rej ection mechanism, especially the role of humoral immunological respons es in the concordant rat to mouse cardiac xenograft model. Lewis rat h earts transplanted into C3H/HeN mice were rejected in 5-6 days. The es sential role of humoral factors in the rejection was demonstrated by h istological analysis of the rejected hearts showing interstitial hemor rhage, scant cellular infiltration, and the dense deposition of mouse IgG, IgM, and C3 on the graft endothelial cells. In addition, mice tha t received hyperimmune serum (serum at the 10th day after transplantat ion) rejected rat hearts hyperacutely. Flow cytometrical analysis usin g cultured donor rat coronary endothelial cells demonstrated the xenor eactive antibodies of all subclasses, but especially strong reactivity of IgM and IgG2a in the serum at rejection. These xenoreactive antibo dies were produced against not only MHC, but also non-MHC antigens on graft endothelial cells. In vivo depletion of L3T4(+) T cells led to t he suppression of xenoreactive antibody production and the prolongatio n of graft survival, indicating that antibody production in this model needs L3T4(+) T cell help.