Journal
CURRENT OPINION IN ORGAN TRANSPLANTATION
Volume 18, Issue 6, Pages 645-651Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0000000000000022
Keywords
immunosuppression; skin immunobiology; tolerance; transplant; vascularized composite allotransplantation
Categories
Funding
- Melina Nakos Foundation
- Musculoskeletal Transplant Foundation
- American Society for Transplantation
- American Society of Transplant Surgeons
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Purpose of reviewVascularized composite allotransplantation (VCA) is increasingly utilized in the restoration of complex injuries and tissue loss. Acute skin-targeted rejection episodes are common and concerns remain regarding the risks of conventional immunosuppression. We review current immunosuppressive regimens for VCA, progress with immunomodulatory and tolerance protocols, and highlight recent advances in cutaneous immunobiology which will have significant implications for future development in the field.Recent findingsAdvances in induction protocols have demonstrated effective prevention of early graft loss in hand transplantation, although long-term outcomes are still pending. Furthermore, recent findings in leukocyte populations within the skin and their mechanisms of communication reveal that considerable numbers of resident T-effector memory cells, including a T-regulatory subset, exist, and that epidermal Langerhans' cells communicate with these cells, mediating both immunity and tolerance to maintain skin homeostasis.SummaryThe majority of VCA centers utilize antibody-mediated induction, followed by double or triple-agent maintenance immunosuppression. A clinical trial of a minimal-immunosuppression protocol based on bone marrow infusion reports encouraging interim results, but long-term follow-up will be required. Skin remains the primary target of rejection in VCA. New data demonstrate extensive T-cell memory resident in skin, and complex interactions between these cells and epidermal Langerhans' cells will have implications for VCA rejection and tolerance, and warrant further investigation in the allogeneic setting.
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