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Órgano oficial de difusión de la Federación Mexicana de Patología Clínica, AC y de la Asociación Latinoamericana de Patología Clínica/Medicina de Laboratorio

2003, Number 3

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Rev Mex Patol Clin Med Lab 2003; 50 (3)

Immunological events mediated by means of cells during the rejection of xenotransplantations. Cellular recognition in xenotransplantation of vascularized organs

Arteaga TG, Guerra-Infante FM

Language: Spanish
References: 73
Page: 129-141
PDF size: 361.21 Kb.


ABSTRACT

Major advances in surgical techniques and the development of new immunosuppressive drugs and strategies of operation have led to transplantation becoming the treatment of choice for end stage organ failure, with patients achieving long term survival and a high quality of life. The cost benefits of transplantation have been well recognized and renal transplantation alone saves huge amounts of money spent on dialysis. The gap between the numbers on waiting lists and the available organs continues to widen as the number of donors declines in many countries. Xenotransplantation has several potential benefits provided the various obstacles can be overcome. The use of pigs as a source of organs would provide an almost unlimited supply. The organs would be available at all times, allowing surgery to be planned and optimally timed, and the damaging effects of brain death on the organs would be avoided. The major obstacle would be the immune reaction of the host to the graft. In cases where antibody and complement-mediated hyperacute rejection of vascularized xenografts has been prevented, acute vascular rejection and acute T cell mediated rejection cause graft lysis. Infiltration leukocytes into the graft execute the latter two rejection modalities. In the first place, the leukocyte extravasation process is governed by adhesion molecules and the chemokine protein family, and the presence of human anti-pig antibodies modulated the migration of leukocytes across porcine endothelium, as well as neutrophil polymorf cells. Likewise, graft face destruction by natural killer cells as well as T cells have been reported. On the other hand, porcine endotelium molecules can trigger both cytokine production and cytolytic activity by NK cells. The T cell mediated xeno response is thought to be direct and indirect recognition of porcine swine leukocyte antigens, class I and II molecules are recognized by CD8+ and CD4+ T cells respectivity. However, the mechanism of destruction by CD4+ T cells is poorly understood. CD4+ T cells are capable of mediating delayed-type hypersensitivity reaction, resulting in graft damage because of the production cytokines in situ as well as direct cytotoxicity. If the problems of immunological rejection can be overcome, there remain concerns that there may be physiological or anatomical incompatibilities or limitations that effect graft function or survival.


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