title: Depletion of recipient CD4+ but not CD8+ T lymphocytes prevents the development of cardiac allograft vasculopathy.
abstract: BACKGROUND
  We have described that chimeric rat hearts bearing recipient-type antigen-presenting cells (APCs) do not reject acutely, but develop cardiac allograft vasculopathy (CAV) in untreated recipients. This suggests that CAV is triggered either by CD8+ direct allorecognition or by CD4+ indirect allorecognition. To determine the allorecognition pathway responsible for CAV in this model, recipients of chimeric hearts underwent either CD8+ or CD4+ T cell depletion.
  
  
  METHODS
  Chimeric hearts were created via bone marrow transplantation in two fully major histocompatibility-mismatched rat strain combinations. DA recipients were thymectomized and treated with Ox8 and Ox38 murine monoclonal antibodies, which deplete CD8+ and CD4+ T cells, respectively. Chimeric PVG hearts bearing DA APCs, abbreviated PVG(DA), were heterotopically transplanted into recipients undergoing thymectomy alone or recipients undergoing thymectomy plus either CD4+ or CD8+ T cell depletion.
  
  
  RESULTS
  PVG(DA) allografts survived 100 days, but developed CAV in thymectomized recipients and in those permanently depleted of CD8+ T cells. In contrast, chimeric hearts transplanted into permanently CD4+ T cell-depleted recipients survived 100 days and demonstrated no evidence of CAV.
  
  
  CONCLUSIONS
  In this specific strain combination, recipient CD8+ T cells are neither necessary nor sufficient for the development of CAV, whereas recipient CD4+ T cells are required for the development of CAV. These findings suggest that CAV is dependent on CD4+ indirect allorecognition and that CD8+ direct allorecognition stimulated by nonprofessional APCs plays a minor role.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Wilson Y
authors.initials: WY
authors.lastname: Szeto
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
authors.forename: Sicco H
authors.initials: SH
authors.lastname: Popma
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosengard
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002102:Cadaver; D002908:Chronic Disease; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects*; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D014184:Transplantation, Homologous