title: Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine.
abstract: BACKGROUND
  Recent studies in mice and patients suggest that posttransplantation induction of autoimmune responses to tissue-specific antigens contributes to the rejection of major histocompatibility complex mismatched allotransplants. The relevance of this phenomenon to the rejection of major and minor histocompatibility-mismatched allografts performed in large-animal models remains to be established.
  
  
  METHODS
  Miniature swine were immunized with cardiac myosin (CM) in Freund's adjuvant and received heterotopic, minor antigen-mismatched heart transplants. T-cell (proliferation and delayed type hypersensitivity [DTH]) and B-cell (antibody) responses specific to CM were measured. The rejection of heart transplants was assessed histologically.
  
  
  RESULTS
  Three of four swine that were immunized with CM before receiving a minor antigen-mismatched heart transplant exhibited potent DTH, T-cell proliferation and antibody responses to CM and rejected their grafts acutely. The fourth swine, which failed to mount a significant DTH response to CM and displayed low and transient anti-CM antibody titers, demonstrated long-term allograft survival.
  
  
  CONCLUSIONS
  This large-animal study supports the relevance of autoimmunity to CM in the rejection of minor antigen disparate cardiac allotransplants.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Veillette
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sahara
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Meltzer
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kim
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosengard
authors.forename: James S
authors.initials: JS
authors.lastname: Allan
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Houser
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Gilles
authors.initials: G
authors.lastname: Benichou
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D000208:Acute Disease; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D024722:Cardiac Myosins / Q000276:immunology*; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007114:Immunization; D008213:Lymphocyte Activation; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D024722:Cardiac Myosins