title: Prevention of chronic renal allograft rejection by soluble CD83.
abstract: BACKGROUND
  Recombinant human soluble CD83 had previously exhibited significant immunosuppressive properties that involved interference with dendritic cell maturation in both mouse and humans, inhibition of autoimmunity in mice, and induction of antigen-specific mouse cardiac allograft tolerance when used in combination with other immunosuppressive drugs. Our current research focus turned to examining the effects of peritransplant soluble CD83 (sCD83) administration on prevention of chronic renal allograft rejection.
  
  
  METHODS
  Fisher344-to-Lewis orthotopic rat renal transplants were performed with sequential recipient killing on postoperative days (PODs) 2, 14, and 140 to examine both the acute and chronic effects of peritransplant sCD83 treatment in rat recipients.
  
  
  RESULTS
  Recipients treated with sCD83 exhibited a marked decrease in IgM and IgG deposition in the graft and antidonor antibody levels in the circulation, as early as POD14 and persisting until POD140. sCD83 treatment also reduced the infiltration of T cells and monocytes into the graft tissue and inhibited intragraft expression of MyD88 and inflammatory cytokine levels during the observation period. sCD83-treated grafts demonstrated normal histology beyond POD140, including dramatic reductions in tubular atrophy and interstitial fibrosis compared with untreated recipients.
  
  
  CONCLUSIONS
  We have demonstrated that peritransplant treatment with recombinant sCD83 attenuates both innate and adaptive immune responses and leads to prevention of chronic rejection in a rat renal transplant model. Because sCD83 is of human origin, the therapeutic approach used in our rodent transplant model holds significant promise for clinical transplantation.
authors.affiliation: Department of Surgery, University of Western Ontario, London, ON, Canada.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Lan
authors.forename: Dameng
authors.initials: D
authors.lastname: Lian
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Arp
authors.forename: Brayden
authors.initials: B
authors.lastname: Charlton
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.forename: Stephen
authors.initials: S
authors.lastname: Brand
authors.forename: Don
authors.initials: D
authors.lastname: Healey
authors.forename: Mark
authors.initials: M
authors.lastname: DeBenedette
authors.forename: Charles
authors.initials: C
authors.lastname: Nicolette
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007136:Immunoglobulins / Q000235:genetics / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D016572:Cyclosporine; D016207:Cytokines; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011994:Recombinant Proteins; D000097802:CD83 Antigen