Experimental study for the clinical application of discordant cardiac xenograft.

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At first, we modified the recipient complement(C) system, especially the alternative pathway, with the anti-complement drug, FUT175 and K76C00H, and evaluated the effects of these drugs in the hyperacute rejection, using guinea-pig to rat and pig to dog discordant cardiac xenograft model. The administration of both FUT175 and K76 resulted in the prolongation of the graft survival in guinea pig to rat model,but the effects of these drugs were abolished by strong natural antibody in pig to dog model. Next, from the point of the modification in the graft side, we investigated the susceptibility to human complement of xeno-erythrocytes (E) in which CD55 or CD59 was incorporated. The efficacy of CD55/CD59-mediated protection of xenogeneic cell from human C differed among the E-species. In both C pathways, E-swine or E-sheep were protected by the incorporated CD55 more effectively than CD59 at both C3 andlate steps. Apart from C system which causes hyperacute xenograft rejection, the antibody response and the cell-mediated immune responses have a important role, in the closely related species combination, such as rat to mouse. We also investigated its rejection mechanism. Our results showed that in vivo treatment with anti-CD4 but anti-CD8 or anti-C receptor antibody lead to a prolongation of graft survival. CD4 T cells are of crucial importance, not only in helper function, but also in the effector phase in the accelerated rejection of rat to mouse xenograft.