Immunological Considerations for Inducing Skin Graft Tolerance

While the first uses of skin transplantation may be found in anecdotal images involving the use of foreign tissue to cover burns and damaged skin, the modern era of skin grafting attempts to understand the phenomenon scientifically. One well documented case describes Joseph E. Murray’s surgical procedure to use skin from a recently deceased person to cover the skin of a pilot who suffered disfiguring burns in 1944 (Murray, 1992) The transplanted skin survived for more than thirty days, despite any predictions of rejection that might have destroyed the tissue in two weeks or less. Murray hypothesized that the procedure was successful because of the weakened state of the recipient’s immune system. Murray continued his interest in transplantation immunology, and ten years later his team was the first to engraft an organ from a living donor, (Murray, 1992). In 1944 Medawar described rejection of allografts, that is, organs or tissues exchanged between individuals of the same species (Medawar, 1944). His pioneering work described the consequences of allograft and autograft transplantation in exquisite detail. He used the rabbit skin model to show differences in acceptance of autografts, using the same individual or same strain as the tissue source, vs. allografts that exchanged skin between different animals of the same species. He further used meticulously measured tissue size as a surrogate marker for skin antigen dose and documented the process of healing for autographs opposed to the “actively acquired immune reactions” that resulted in the necrosis of allografts. R. E. Billingham (1959) reviewed the fate of engrafted tissue that is rejected by the host in light of the then recently discovered major histocompatibility complex in the mouse (MHC). The MHC genes encode cell surface proteins that allow the immune system to discriminate between its own cells and foreign cells. Billingham referenced the use of isogenic mouse strains wherein each animal of the strain has identical MHC genes, and these animal models facilitated the understanding of graft versus host disease, rejection mediated by immunocompetent cells within a graft (Billingham, 1959). Billingham, Brent, and Medawar (1953) described immunological tolerance that is actively acquired following prenatal exposure to foreign tissue in a mouse model. This phenomenon described the survival of engrafted tissue, whereas the same tissue generated immunity resulting in graft destruction when transplanted in the adult. After eight weeks, the tolerant mice were challenged with adult skin of the same donor origin as the primary transplant, in order to evaluate the persistence of tolerance. These experiments documented the utility of