XENOTRANSPLANTATION - IMMUNE BARRIERS BEYOND HYPERACUTE REJECTION

1. The use of organs from animal donors (xenotransplantation) is a pot ential solution tal the chronic shortage of allogeneic organs and curr ently the pig is thought to be the most suitable donor for man, Howeve r, porcine organs are rejected rapidly by a vascular process called hy peracute rejection which has so far prevented clinical xenotransplanta tion, Although it is likely that this barrier will be overcome in the near future by the application of novel strategies, probably involving the use of organs from transgenic pigs, data from animal models indic ate that multiple other immune mechanisms will contribute to the rejec tion of xenografts, 2, We have described two aspects of these immune m echanisms, First, the phenomenon of 'accommodation', whereby xenograft s acquire in vivo resistance to vascular rejection, has been explored in an in vitro model utilizing immortalized porcine endothelial cells. The results indicate that human anti-pig antibodies induce a concentr ation-dependent and time-dependent change in porcine endothelial cells compatible with the development of accommodation. 3, Secondly, the in vitro human anti-porcine T-cell response has been documented in detai l, with particular emphasis on quantitative and qualitative comparison s with the in vitro T-cell alloresponse. The results of this work, whi ch indicate that the response to porcine xenografts is likely to be si gnificantly stronger than that against allografts, have important impl ications for the level of conventional immunosuppression that may be n ecessary to prevent xenograft rejection, and provide an important basi s for the development of strategies to promote xenograft-specific immu nosuppression and tolerance.