title: Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy.
abstract: BACKGROUND
  In patients with acute myocarditis and dilated cardiomyopathy (DCM), we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen-presenting cells (APCs) as well as the main signal provided by binding of T-cell receptors to the antigen.
  
  
  RESULTS
  To investigate the roles of the costimulatory molecules B7-1, B7-2, and CD40 in the development of acute myocarditis and DCM, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, because both killer lymphocytes are thought to damage B7-1-expressing APCs. We found that B7-1, B7-2, and CD40 were moderately to strongly expressed in the cardiac myocytes of patients with acute myocarditis. Weak to moderate expression of these antigens was also found in the cardiac myocytes of patients with DCM. There was infiltration of perforin-expressing CTLs and NK cells in the myocardial tissues of patients with acute myocarditis and DCM.
  
  
  CONCLUSIONS
  Our findings strongly suggest that expression of B7-1, B7-2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Seko
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Ishiyama
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Kasajima
authors.forename: M
authors.initials: M
authors.lastname: Hiroe
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Ishiwata
authors.forename: S
authors.initials: S
authors.lastname: Kawai
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006352:Heart Ventricles; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin