Immune responses in transplantation: application to composite tissue allograft

After announcements of successful hand, larynx, knee, muscle, nerve, and, most recently, face transplantation, composite tissue allografts (CTAs) have been introduced into the armamentarium of plastic and reconstructive surgery. Because the microsurgical techniques required to perform CTA transplants are well established and used in daily practice by plastic surgeons, the immunologic aspects of transplantation remain of great interest to plastic surgeons. CTAs offer a unique potential for coverage of large multitissue defects; however, compared with the relatively homogenous tissue of solid organ transplants, the heterogenicity of tissue components of CTA may generate high immunologic responses. Although modern immunosuppressive agents significantly improve successful allograft acceptance, chronic allograft rejection as well as immunosuppressive drug toxicity remain major problems in the clinical practice of transplantation. The major goal of transplantation immunology is to develop tolerance to allograft transplants and long-term drug-free survival. Several experimental protocols have been designed to develop tolerance; however, none of them have been proved to induce tolerance in clinical transplantation. This review outlines the mechanisms of allograft acceptance and rejection and describes the barriers to transplantation tolerance based on our current knowledge as it applies to solid organs and CTA transplants. The review also describes innovative immunosuppressive protocols.