title: Inhibition of chronic vascular rejection by donor-specific blood transfusion is associated with a reduction in transforming growth factor-beta1 expression.
abstract: BACKGROUND
  Concentric intimal thickening and the infiltration of inflammatory cells in cardiac allografts are the pathological hallmark characteristics of chronic vascular rejection (CVR), the leading cause of long-term graft failure. The precise mechanisms involved in the development and pathogenesis of CVR remain elusive. In the PVG-R23 to PVG-RT1u rat model of CVR, prior administration of a donor-specific transfusion (DST) was previously shown to prolong graft survival indefinitely and abolish the vascular lesions associated with CVR. The present study investigates in more depth the underlying mechanisms involved in the subsequent prolongation of allograft survival and inhibition of CVR by DST.
  
  
  METHODS
  R23 heart grafts were monitored in nontransfused and transfused RT1u recipients injected 2 weeks before transplantation with 1.5 ml of R23 blood. Severity of arteriosclerosis, transplant infiltrate, transforming growth factor (TGF)-beta1 protein expression within the graft, plasma TGF-beta1 levels, class II MHC expression, tenascin protein expression, and serum alloantibody levels were measured.
  
  
  RESULTS
  There was no significant difference in donor MHC class II, myocardial TGF-beta1, or tenascin expression between DST and non-DST-treated recipients. However, DST-pretreated recipients showed greatly reduced histological evidence of CVR and had lower titers of R23-specific IgG subclasses. Furthermore, DST-treated allograft recipients showed significant decreases in circulating TGF-beta1 levels and a reduction in TGF-beta1 and tenascin expression within coronary arteries of the allografts.
  
  
  CONCLUSIONS
  The results suggested that DST inhibited CVR by altering and regulating the expression of TGF-beta1, thereby preventing the fibrogenic effects associated with TGF-beta1.
authors.affiliation: Immunology Research Group, School of Biological Sciences, and Department of Medicine, University of Manchester, Manchester, United Kingdom.
authors.forename: Emma A O
authors.initials: EA
authors.lastname: Shittu
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Yang
authors.forename: Ian S D
authors.initials: IS
authors.lastname: Roberts
authors.forename: Eric B
authors.initials: EB
authors.lastname: Bell
authors.forename: Paul
authors.initials: P
authors.lastname: Brenchley
authors.forename: Trudie
authors.initials: T
authors.lastname: Roberts
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wood
mesh_terms: D000208:Acute Disease; D000818:Animals; D001803:Blood Transfusion; D005786:Gene Expression Regulation / Q000276:immunology; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D051381:Rats; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1