title: Potential of T-regulatory cells to protect xenografts.
abstract: OBJECTIVE
  Immunological barriers still preclude clinical xenotransplantation. The protective role of CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Treg) in allotransplantation is well described and, therefore, could represent a promising therapeutical tool for xenotransplantation. This review addresses the latest findings on Treg in xenotransplantation research.
  
  
  RESULTS
  In vivo, costimulation blockade-based strategies including anti-CD154 monoclonal antibodies (mAbs) in combination with rapamycin or anti-LFA-1 mAb prolonged both concordant and discordant islets xenografts survival in a Treg-dependent manner. In vitro, IL-10 secretion was shown to be critical for the suppression of xenogeneic responses mediated by Treg. Moreover, transgenic expression of inducible costimulator-immunoglobulin or PD-L1 on porcine endothelial cells inhibited human T-cell proliferation in vitro and was associated with the induction of Treg and IL-10 secretion. CXCR3 mediated the recruitment of Treg to pig endothelium. Finally, the recruitment of human Treg was enhanced by the immobilization of human CCL17 on pig endothelium.
  
  
  CONCLUSIONS
  There is increasing evidence for the potential of CD4(+)CD25(+)Foxp3(+) Treg to protect xenografts. Induction of Treg in recipients and/or recruitment of human Treg to pig endothelium may represent novel strategies to prevent cell-mediated rejection in pig-to-human xenotransplantation.
authors.affiliation: Division of Clinical Immunology and Allergology, Department of Internal Medicine, University Hospital and Medical Faculty, Switzerland. yannick.muller@unige.ch
authors.forename: Yannick D
authors.initials: YD
authors.lastname: Muller
authors.forename: Driss
authors.initials: D
authors.lastname: Ehirchiou
authors.forename: Déla
authors.initials: D
authors.lastname: Golshayan
authors.forename: Leo H
authors.initials: LH
authors.lastname: Buhler
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Seebach
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology; D013552:Swine; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D020123:Sirolimus