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Expression of functional T‐cell markers and T‐cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy
Author(s) -
Noutsias Michel,
Rohde Maria,
Göldner Katrin,
Block Andrea,
Blunert Katja,
Hemaidan Lara,
Hummel Michael,
Blohm JanHenrik,
Lassner Dirk,
Kühl Uwe,
Schultheiss HeinzPeter,
Volk HansDieter,
Kotsch Katja
Publication year - 2011
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfr014
Subject(s) - granulysin , foxp3 , granzyme a , myocarditis , medicine , cytotoxic t cell , immunology , granzyme b , perforin , t cell , cd8 , immune system , biology , biochemistry , in vitro
Aims To quantify and functionally characterize the intramyocardial T‐cells in endomyocardial biopsies (EMBs) from patients presenting with acute myocarditis (AMC) and dilated cardiomyopathy (DCM). Methods and 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.