title: Inhibition of chronic rejection by antibody induced vascular accommodation in fully allogeneic heart allografts.
abstract: BACKGROUND
  The potential role of altered antibody responses as an effector protective mechanism to induce graft accommodation has been widely investigated in xenogeneic responses. Here we investigate the protective effects of antibody binding to vascular endothelium in a fully mismatched allogeneic model of heart transplantation.
  
  
  METHODS
  ACI recipients of WF cardiac grafts were treated either with allochimeric [alpha1h ]-RT1.A class I major histocompatibility complex (MHC) extracts (1 mg/rat, p.v. day 0) or high dose of CsA (10 mg/kg/day, p.o., day 0-6). Cardiac allografts were evaluated at 100 days posttransplant by immunohistology for evidence of chronic rejection and/or vascular accommodation. Activation of apoptotic or antiapoptotic mechanisms was verified by DNA fragmentation (TUNEL) analysis.
  
  
  RESULTS
  Allochimeric therapy resulted in inhibition of chronic rejection, absence of neointimal formation and induction of vascular accommodation of fully allogeneic WF hearts in ACI hosts. Such accommodation was evident by IgG and IgM vascular endothelial binding and marked reduction of DNA fragmentation. In contrast, CsA therapy resulted in marked neointimal proliferation, without evidence of vascular accommodation. Immunohistochemical analysis failed to demonstrate vascular endothelial antibody binding. Further, severe chronic rejection following CsA treatment was accompanied by marked DNA fragmentation.
  
  
  CONCLUSIONS
  Alteration of humoral immunity induces vascular accommodation in allogeneic transplantation. Vascular accommodation is the underlying mechanism for inhibition allograft vasculopathy following allochimeric MHC class I therapy.
authors.affiliation: The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-7054, USA.
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Semiletova
authors.forename: Xiu-Da
authors.initials: XD
authors.lastname: Shen
authors.forename: Boris
authors.initials: B
authors.lastname: Baibakov
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Feldman
authors.forename: Kaushik
authors.initials: K
authors.lastname: Mukherjee
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Frank
authors.forename: Stainslaw M
authors.initials: SM
authors.lastname: Stepkowski
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
authors.forename: Rafik M
authors.initials: RM
authors.lastname: Ghobrial
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D017209:Apoptosis / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007165:Immunosuppression Therapy / Q000379:methods*; D007518:Isoantibodies / Q000032:analysis; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies