title: Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy.
abstract: OBJECTIVE
  To quantify and functionally characterize the intramyocardial T-cells in endomyocardial biopsies (EMBs) from patients presenting with acute myocarditis (AMC) and dilated cardiomyopathy (DCM).
  
  
  RESULTS
  Expression of genes characterizing Th1 [interferon (IFN)γ, Tbet-1, Eomesodermin, interleukin (IL)-27], Th2 (IL-4, IL-5, GATA3), Th17 (IL-17), regulatory [regulatory T-cells (Treg); FoxP3, TGFβ, IL-10], anergic (GRAIL), and cytotoxic T-cells (CTLs: Perforin, Granulysin, Granzyme A), as well as of functional T-cell receptor Vbeta (TRBV) families were investigated in EMBs from AMC patients (n= 58) and DCM patients (n= 34) by pre-amplified real-time reverse transcription-polymerase chain reaction. These data were compared with EMBs from n= 19 controls. Expression of CD3d, CD3z, and TRBC (T-cell receptor beta constant region) were associated with the immunohistological diagnosis of inflammatory cardiomyopathy (DCMi). In EMBs from DCM patients with increased CD3d expression, significantly increased markers of Th1 (IFNγ, T-bet, Eomesodermin), regulatory T-cells (Treg; FoxP3, TGFβ), and cytotoxic T-cells (CTLs: Perforin, Granulysin, Granzyme A) were present, while no differential polarization of T-cells was found in EMBs form AMC patients. A differential dominance of distinct functional TRBV families was associated with different cardiotropic viruses: TRBV 11 and 24 with Parvovirus B19; TRBV4, 10 and 28 with human herpes virus type 6; and TRBV14 for Coxsackie virus, respectively.
  
  
  CONCLUSIONS
  The T-cell infiltrates in human DCMi are characterized by differential expression of functional T-cell markers indicating Th1, Treg, and CTLs, while no major role could be confirmed for Th17. The virus-associated differential TRBV dominance suggests an antiviral specificity of virus-induced T-cell responses in human DCMi.
authors.affiliation: Department of Cardiology and Pneumonology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany. michel.noutsias@staff.uni-marburg.de
authors.forename: Michel
authors.initials: M
authors.lastname: Noutsias
authors.forename: Maria
authors.initials: M
authors.lastname: Rohde
authors.forename: Katrin
authors.initials: K
authors.lastname: Göldner
authors.forename: Andrea
authors.initials: A
authors.lastname: Block
authors.forename: Katja
authors.initials: K
authors.lastname: Blunert
authors.forename: Lara
authors.initials: L
authors.lastname: Hemaidan
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Jan-Henrik
authors.initials: JH
authors.lastname: Blohm
authors.forename: Dirk
authors.initials: D
authors.lastname: Lassner
authors.forename: Uwe
authors.initials: U
authors.lastname: Kühl
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Katja
authors.initials: K
authors.lastname: Kotsch
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000821:virology; D004699:Endocardium / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology* / Q000821:virology; D009206:Myocardium / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016693:Receptors, Antigen, T-Cell, alpha-beta