Fundamental Immunology of Skin Transplantation and Key Strategies for Tolerance Induction
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Fundamental Immunology of Skin Transplantation and Key Strategies for Tolerance Induction Junyi Zhou • Weifeng He • Gaoxing Luo Jun Wu
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Received: 17 October 2012 / Accepted: 26 April 2013 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013
Abstract Transplantation of allogeneic or xenogeneic skin grafts can evoke strong immune responses that lead to acute rejection of the graft tissues. In this process, donor-derived dendritic cells play crucial roles in the triggering of such immune responses. Both the innate and acquired host immune systems participate in graft rejection. At present, the rejection of skin grafts cannot be well-controlled by ordinary systemic immunosuppression therapy. Although several strategies for the long-term survival of allogeneic or xenogeneic skin grafts have been demonstrated in animal models, the induction of long-term tolerance to skin grafts is still a great challenge in clinical settings. In this article, we review the progress in the understanding of immune responses to skin grafts and discuss the possible methods that can decrease the immunogenicity of graft tissues and improve the survival of skin grafts, especially those included in preoperative pre-treatments. Keywords
Skin transplantation Immunology
Introduction The successful transplantation of allogeneic organs and tissues has significantly improved the outcomes for patients with severe organ dysfunctional diseases and is one of the greatest surgical and immunological achievements of the twentieth century. J. Zhou W. He G. Luo J. Wu (&) State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, The Third Military Medical University, Chongqing, China e-mail: [email protected] W. He J. Wu Chongqing Key Laboratory for Proteomics of Diseases, Chongqing 400038, China
The transplantation of allogeneic skin grafts is an important therapy for patients with major burns or chronic refractory wounds. However, allogeneic skin grafts evoke potent immune responses. Following the transplantation of skin onto a healthy MHC-mismatched recipient, a quick immune rejection process will lead to the failure of the graft within 10–14 days (Richters et al. 2005) with characteristic skin tissue destruction. Allogeneic skin grafts are rejected in a short time period of approximately 20–30 days, even if grafts are placed over the fully excised burn wound base (Bravo et al. 2000; Hansbrough et al. 1997). This process could hardly be controlled by currently available immunosuppressive agents (Gardner 1995). To date, allogeneic skin grafts serve mainly as temporary biological wound dressings that provide a suitable environment for the survival and expansion of autologous small patch or micro skin grafts (Kreis et al. 1989). In the clinic, autologous skin transplantation is the only viable means of achieving permanent closure of massive wounds and the restoration of skin function. Although great achievements have been made in the understanding of i
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