Porcine livers perfused with human blood mount a graft-versus-"host" reaction.
Rees MA., Butler AJ., Davies HFS., Bolton E., Wight DGD., Skepper J., White DJG., Friend PJ.
BACKGROUND: A major focus of xenotransplantation research is the interaction between human immune effector mechanisms and porcine tissues. We present evidence that a transplanted porcine organ might also mount a significant immune response to a human recipient. METHODS: Isolated porcine livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis. ELISA was used to determine the amount and class of porcine immunoglobulin in human blood after xenoperfusion. Flow cytometry was used to determine the specificity and class of porcine immunoglobulin in human blood after xenoperfusion and to determine whether porcine immunoglobulins had bound to the human lymphocytes in the blood perfusing the porcine livers. Electron microscopy was used to evaluate the interaction of porcine Kupffer cells and human erythrocytes. RESULTS: Over the course of 72 hr of extracorporeal perfusion of porcine livers with human blood, the hematocrit fell progressively to as low as 2.5% of starting values, a phenomenon not seen in experiments using porcine blood. We have demonstrated both porcine complement and immunoglobulin in the human blood after xenoperfusion. The porcine antibodies in the human blood have specificity for human lymphocyte antigens. In fact, with increasing duration of perfusion, 40% of the xenoperfusions showed increasing titers of porcine antibodies with specificity for human lymphocyte antigens suggesting a response by primed porcine lymphocytes. However, the majority of erythrocytes are extracted directly by Kupffer cells in the liver. CONCLUSIONS: These data demonstrate the ability of porcine livers to generate both a humoral and cellular graft versus host response to human cells.