Tolerance and future directions for composite tissue allograft transplants: part II

After studying this article, the participant should be able to: 1. Discuss the definition and basic aspects of tolerance as applied to clinical practice. 2. Understand the role of donor bone marrow cells for tolerance induction in composite tissue allograft. 3. Understand the role of passenger leukocytes in allograft acceptance and rejection. 4. Understand the tolerogenic role of dendritic cells and regulatory cells in composite tissue allograft transplants. 5. Understand modern approaches to transplantation tolerance and their applicability to composite tissue allograft transplants.

The introduction of composite tissue allograft transplants into clinical practice has become reality because of well-established microsurgical techniques. However, the success of composite tissue allograft transplants is still dependent on chronic immunosuppression. Clinically applicable protocols for tolerance induction in composite tissue allograft would eliminate the need for lifelong immunosuppression. The major goal of transplantation immunology is to develop immunologic nonresponsiveness (tolerance) to allograft transplants and long-term drug-free survival. A number of protocols have been designed to develop tolerance in experimental systems; however, none of them has been translated to clinical transplantation. In this review, the authors discuss current knowledge and strategies used for tolerance induction and the role of passenger leukocytes for allograft acceptance and rejection. Tolerogenic properties of dendritic cells and immunotherapy with regulatory T cells are introduced as having future potential for tolerance induction in solid organ and composite tissue allograft transplants. The induction of donor-specific tolerance would generate new options for the application of composite tissue allograft transplants and may be considered as a future direction in plastic and reconstructive surgery.