[Xenotransplantation: physiopathology of hyperacute and differentiated rejection, and therapeutic perspectives].
The mechanisms of xenograft rejection involved in closely related species of donors and recipients are not the same as in disparate combinations. When the donor and the recipient are phylogenetically close, such as the monkey and the human being, the rejection of xenografts is essentially mediated by a cellular immune response, and is clinically similar to a strong allograft rejection. When the donor and the recipient belong to widely disparate species, such as in the pig-to-human combination, the graft is destroyed by a hyperacute rejection before a cellular rejection has started. Hyperacute rejection is triggered by the fixation of the recipient's preformed antibodies on the graft endothelium, and subsequent activation of the recipient's complement. The activation of endothelial cells that ensues leads to the formation of an extensive thrombosis within the graft and to its necrosis within minutes or hours after grafting. When hyperacute rejection is overcome by means of complement inhibitors, a delayed vascular rejection occurs within 36 to 48 hours, mainly involving antibody-dependent cellular cytotoxicity and contributing to the extension of the thrombosis. Both hyperacute and delayed vascular rejections can be prevented by depletion of preformed antibodies, inhibition of complement activation, or by masking the dominant xeno-epitope Gal alpha 1,3 Gal. Transgenic pigs expressing molecules that inhibit xenogeneic rejection are being produced. However, prior to any clinical use, the infectious risks, and particularly the viral risk must be evaluated.
Malassagne
B
B
Laboratoire d'immunologie, AP-HP, facult¿e Cochin-Port-Royal, universit¿e Paris V-Ren¿e-Descartes, France.
Calmus
Y
Y
Houssin
D
D
Weill
B
B
D000208:Acute Disease; D000818:Animals; D003167:Complement Activation; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000882:Haplorhini; D006801:Humans; D007111:Immunity, Cellular; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology / Q000502:physiology
La x¿enotransplantation, physiopathologie du rejet suraigu et diff¿er¿e, et perspectives th¿erapeutiques.