Hand transplants and the mandate for tolerance.
OBJECTIVE
The field of vascularized composite allograft (VCA) to achieve its full potential will require induction of tolerance. This review will introduce a new method of potential inducing tolerance in hand transplantation.


RESULTS
Hand transplantation is never a life-extending transplant. This fact resulted in considerable debate both for and against the use of immunosuppression for nonlife-extending transplants. There is considerable debate about the ethics of hand transplantation. There is now consensus that nonlife-extending transplants are acceptable in properly selected patients. However, ideally, hand transplants should not receive life-long immunosuppression. Therefore, attempts to achieve drug-free tolerance through nonlife-endangering therapies are warranted. To this end, we propose implementation of tolerizing therapy long after periinflammation has subsided and drug minimization has proven successful. Evidence that short-term treatment with low doses of IL-2 or a long-lived IL-2 immunoglobulin (Ig) can tilt the balance of immunity from tissue destructive to tolerance come from preclinical demonstrations in mouse and nonhuman primate models of autoimmunity and/or transplantation and even more recent clinical trials.


CONCLUSIONS
We believe that with the proper use of low-dose IL-2 given at an opportune time in the inflammatory process of transplant that reduce immunosuppression and even tolerance can be induced in hand transplantation. We propose that tolerance can be inducted after a long period of conventional treatment to avoid 'tolerance-hindering' adverse inflammation that occurs in the posttransplant period. With abatement of posttransplant inflammation and with time, we will institute low-dose IL-2-based therapy to support the proliferation, viability and functional phenotype of regulatory T cells.
aDepartment of Medicine, Harvard Medical School, Transplant Institute, Beth Israel Deaconess Medical Center bDivision of Plastic Surgery, Department of Surgery cDivision of Dermatopathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Maria
M
Koulmanda
Bohdan
B
Pomahac
Zhigang
Z
Fan
George F
GF
Murphy
Terry B
TB
Strom
D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D063987:Hand Transplantation; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology
D007376:Interleukin-2