Xenogeneic (Molecular Biology)

Acceptance of an organ graft from one donor to a recipient is strictly conditioned by their respective genetic constitutions. Identity defines syngeneic conditions, which occur with monozygous twins or animals from the same inbred strain. Because there is no genetic difference between donor and recipient, the graft is accepted. Whenever the donor and the recipient belong to the same animal species, but differ in their genetic constitution, the allogeneic graft is rejected after 10 to 12 days. Allogeneic graft rejection is an immunological reaction, because it is specific, mediated essentially by cytotoxic T lymphocytes, and controlled by molecules of the major histocompatibility complex (MHC): HLA in humans and H2 in mice. Secondary responses are apparent by an accelerated rejection after a second graft from the same genetic origin as the first one. A xenogeneic donor and recipient belong to different animal species. In this case, the rejection is immediate and particularly violent. The mechanisms of xenogeneic graft rejection are numerous and complex. Hyperacute rejection is due to the presence of natural antibodies that bind to the endothelium, thereby inducing complement fixation, activation of the endothelium, and initiation of blood clotting. Many efforts have been made in the recent past to understand the mechanism of xenogeneic rejection and to define strategies to overcome it, because it might provide a valuable source of organs for human transplantation. So far, significant results have been gained at least for the hyperacute phase, but enormous difficulties are still to be solved. A second immunological barrier is that of the delayed xenograft/acute vascular rejection, which is still not fully understood. Third, rejection mechanisms similar to those encountered in allograft rejection are also operating, with an increased efficiency. All these barriers have to be solved before xenograft really become a reality. To date, no classical immunosuppressive drug can prevent such rejection. The present efforts aim to induce specific unresponsiveness to the most antigenic foreign constituents, but this remains a very difficult task.