title: Vascularized composite allograft rejection is delayed by intrajejunal treatment with donor splenocytes without concomitant immunosuppressants.
abstract: BACKGROUND
  Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection.
  
  
  METHODS
  Lewis rats (n = 12; TREATED) received seven daily intrajejunal treatments of 5 × 10(7) splenocytes from semiallogeneic Lewis-Brown-Norway rats (LBN) or vehicle (n = 11; SHAM). Recipients' immune responses were assessed by mixed lymphocyte reaction (MLR) against donor antigen and controls. Other Lewis (n = 8; TREATED/VCA) received LBN hindlimb VCA and daily intrajejunal treatments of 5 × 10(7) LBN splenocytes, or LBN VCA without treatment (n = 5; SHAM/VCA), until VCAs rejected. Recipients' immune responses were characterised and VCAs biopsied for histopathology. Immunosuppressants were not used.
  
  
  RESULTS
  LBN-specific hyporesponsiveness was induced only in treated Lewis recipients. Treatment significantly reduced MLR alloreactivity, significantly reduced VCA rejection on histopathology, and significantly delayed clinical VCA rejection (P < 0.0005; TREATED/VCA mean 9.6 versus 6.0 days for SHAM/VCA). Treatment significantly increased immunosuppressive IL-10/IL-4/TGF-β production and significantly decreased proinflammatory IFN-γ/TNF-α.
  
  
  CONCLUSIONS
  Jejunal exposure to antigen conferred donor specific hyporesponsiveness that delayed VCA rejection. This method may offer a low-risk adjunctive treatment option to help protect VCAs from rejection.
authors.affiliation: Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, Taipei, Taiwan.
authors.forename: Christopher Glenn
authors.initials: CG
authors.lastname: Wallace
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Hsiang-Chen
authors.initials: HC
authors.lastname: Yang
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
authors.forename: Ren-Chin
authors.initials: RC
authors.lastname: Wu
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Huang
authors.forename: Jeng-Yee
authors.initials: JY
authors.lastname: Lin
authors.forename: Fu-Chan
authors.initials: FC
authors.lastname: Wei
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007583:Jejunum / Q000601:surgery; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D009132:Muscles / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma