Evolutionary and immunological aspects of xenotransplantation

Immunological aspects in xenotransplantation are directly linked to evolutionary aspects. The immunological network with its high antigen specificity and species-specific interactions was developed to fight against the host's outside world including xenografts. The tremendous amount of reaction and mechanisms triggered by the performed natural antibody-endothelial cell reaction clearly indicates that only basic changes might overcome these problems. Even the introduction of transgenic donors might not be sufficient to modify more than one parameter, for example, complement activity. Total depletion of preformed natural antibodies is not compatible with normal life and the regulation of hormones and enzymes under xenogeneic conditions has just been discovered. Cellular mechanisms depend, as far as we know, on the delicate system of receptors, interleukins, and MHC antigens. From today's very early results we know that major changes exist already between closely related species. The investigation of xenogenic mechanisms has opened a totally new field of immunological interactions. Up to now there are no signs of solution to bridge clinically relevant times with xenogenic organs from widely divergent suitable donors with promising quality of life.