The Immunologic Response to Xenografts

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Abstract
The rejection of xenografts is clearly an immunologic phenomenon, since in the absence of an immune response, animals accept transplants even across widely disparate xenogeneic barriers. For example, nude mice, in which the absence of the thymus leads to defective T-cell immunity, have been shown to accept xenogeneic skin grafts ( Manning and others 1973 ), even to the point of growing chicken feathers. Similarly, some of the lymphohematopoietic compartments in severe combined immune-deficient (scid) mice can be repopulated by highly disparate xenogeneic hematopoietic cells ( Mosier and others 1988 ; McCune and others 1988 ). In theory, eliminating the immune response to a xenograft should be sufficient to assure its success. This premise is of more than just theoretical importance to the field of xenotransplantation, since there certainly might have been other, non-immunologic barriers that could have prevented xenotransplantation even in the absence of an immune response. For example, the cell surfaces of xenogeneic tissues might have been physiologically incompatible, or the red cells of the recipient might have been physiologically incapable of delivering oxygen to xenogeneic tissues or even unable to negotiate xenogeneic capillaries. Nevertheless, at least between mammalian species, it now seems likely that the immune response is the barrier of greatest importance.