Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection.
Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II alleles associated with susceptibility to type 1 diabetes (HLA-DR4 and HLA-DQA1*04/05/06 alleles) were remarkably infrequent in IDC patients (p < 0.005), thus suggesting that they might confer protection against IDC. Finally, mRNA for interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha was detected in the cardiac specimens, although at a lower level compared with specimens from hearts without signs of viral infections. We conclude that CVB infection of the human myocardium is associated with a selective, yet polyclonal activation of different T-cell subsets in genetically susceptible individuals. This immune response may play a critical role in modulating disease progression after viral infections.
Luppi
Patrizia
P
Department of Pediatrics, Division of Immunogenetics, University of Pittsburgh School of Medicine, PA, USA.
Rudert
William
W
Licata
Anna
A
Riboni
Sara
S
Betters
Dawn
D
Cotrufo
Maurizio
M
Frati
Giacomo
G
Condorelli
Gianluigi
G
Trucco
Massimo
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000276:immunology* / Q000821:virology; D002648:Child; D002522:Chlorocebus aethiops; D022801:Complementarity Determining Regions / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004279:DNA, Viral / Q000302:isolation & purification; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D015329:Gene Rearrangement, T-Lymphocyte; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000209:etiology / Q000276:immunology* / Q000821:virology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014709:Vero Cells / Q000821:virology
D022801:Complementarity Determining Regions; D016207:Cytokines; D004279:DNA, Viral; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta