title: Vascularized composite allotransplantation: towards tolerance and the importance of skin-specific immunobiology.
abstract: OBJECTIVE
  Vascularized 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.
  
  
  RESULTS
  Advances 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: aVascularized Composite Allotransplantation Laboratory, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School bDepartment of Biology, Emmanuel College, Boston, Massachusetts, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Leonard
authors.forename: Josef M
authors.initials: JM
authors.lastname: Kurtz
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cetrulo
mesh_terms: D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous; D063986:Vascularized Composite Allotransplantation
chemical_list: D007166:Immunosuppressive Agents