Immunopathology of Organ Transplantation

The early history of transplantation is born of legends. The Saints Cosmas and Damian, who lived in the third century allegedly, treated a white patient by removing one of his legs and by grafting that of a black man who had died the same day (Figure 1.1) (1). In modern times, many experimental transplantations, mostly in dogs and cats and then in humans, were attempted in the twenties and thirties of the past century. Some of the pioneers of this era were Carrel, Jaboulay, and Voronoy. As can be expected, most of these trials ended in failures. From the shaping work of Sir Peter B.Medawar, we now know that the failure of organ transplantation is due to immunologic reactions.Medawar et al. cited cases of patients with severe burns: autologous skin grafts healed in, but not allogeneic grafts, which were rejected, and in an accelerated fashion when taken repeatedly from the same donor (2). These observations led to extensive animal experimentations in this area. As a result, a number of fundamental facts about organ transplantation became apparent – 1) a graft may be recognized as antigenic, and it may also be a source of immune cells; 2) this two-way immune response between recipient and donor necessitates the need for immunosuppression for the survival of the graft and the host; and 3) the ultimate goal of many of our efforts should be the induction and maintenance of immunologic tolerance. The investigation of immunogenicity between grafts was discovered serendipitously. George Snell developed inbred mice, by consecutive brother-sister mating for studying tumor genetics. He observed that tumor grafts were accepted between inbred animals but not between animals of different strains (3). The same pattern of tissue acceptance and rejection was true for normal tissues. Snell in collaboration with Peter A. Gorer termed the underlying gene locus histocompatibility 2, or H-2. Further analysis revealed the locus to be genetically complex and the concept of the major histocompatibility complex (MHC) was born, providing the foundation for transplantation immunology