Complement and target cells belong to the same species after liver xenografting: protection from hyperacute rejection.

L IVER xenografting implies that most of the complement (C) in the recipients will be produced by the graft. It is known that membrane-bound proteins have the property of homologous restriction; ie. they inhibit MACmediated lysis only when the terminal C components are from the same species as the cells on which these proteins are expressed. I To test the hypothesis that this could be a mechanism of protection from hyperacute rejection, we transplanted hamster hearts into stable hamster-to-rat liver xenograft recipients (OL T). Minutes later, hyperimmune serum (HS) obtained from untreated hamster heart xenograft recipients was given intravenously (lV}-either unaltered or C-inactivated by heating at 56°C for 30 minutes. Survival of the hamster hearts is shown in Table I. Different dilutions of absorbed sera were tested in their ability to lyse hamster or mouse lymphocytes in a C-dependent cytotoxicity assay. Hamster serum did not lyse hamster cells. While antihamster HS and normal rat serum produced efficient lysis of hamster lymphocytes. that produced by OL T serum was poor. In contrast. OL T serum caused efficient lysis of mouse target cells. In conclusion. the homology of C and target cells represents a novel mechanism of protection that the liver confers to other organs.