title: Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy.
abstract: Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: P
authors.initials: P
authors.lastname: Luppi
authors.forename: A
authors.initials: A
authors.lastname: Licata
authors.forename: C
authors.initials: C
authors.lastname: Haluszczak
authors.forename: W A
authors.initials: WA
authors.lastname: Rudert
authors.forename: G
authors.initials: G
authors.lastname: Trucco
authors.forename: F X
authors.initials: FX
authors.lastname: McGowan
authors.forename: D
authors.initials: D
authors.lastname: Finegold
authors.forename: G J
authors.initials: GJ
authors.lastname: Boyle
authors.forename: M
authors.initials: M
authors.lastname: Trucco
mesh_terms: D000956:Antigens, Viral / Q000032:analysis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000235:genetics*; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006683:HLA-DQ Antigens / Q000145:classification; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006650:Histocompatibility Testing; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009205:Myocarditis / Q000276:immunology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010849:Picornaviridae / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma