Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection

Patrizia Luppi; William Rudert; Anna Licata; Sara Riboni; Dawn Betters; Maurizio Cotrufo; Giacomo Frati; Gianluigi Condorelli; Massimo Trucco

doi:10.1016/s0198-8859(02)00798-x

Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection

Hum Immunol. 2003 Feb;64(2):194-210. doi: 10.1016/s0198-8859(02)00798-x.

Authors

Patrizia Luppi¹, William Rudert, Anna Licata, Sara Riboni, Dawn Betters, Maurizio Cotrufo, Giacomo Frati, Gianluigi Condorelli, Massimo Trucco

Affiliation

¹ Department of Pediatrics, Division of Immunogenetics, University of Pittsburgh School of Medicine, PA, USA.

PMID: 12559622
DOI: 10.1016/s0198-8859(02)00798-x

Abstract

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.

MeSH terms

Adolescent
Adult
Aged
Animals
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cardiomyopathy, Dilated / etiology
Cardiomyopathy, Dilated / immunology*
Cardiomyopathy, Dilated / virology
Child
Chlorocebus aethiops
Complementarity Determining Regions / genetics
Cytokines / biosynthesis
Cytokines / genetics
DNA, Viral / isolation & purification
Diabetes Mellitus, Type 1 / genetics
Enterovirus B, Human / pathogenicity*
Enterovirus Infections / complications
Enterovirus Infections / immunology*
Enterovirus Infections / virology
Female
Gene Expression Profiling
Gene Frequency
Gene Rearrangement, T-Lymphocyte
Genes, T-Cell Receptor alpha
Genes, T-Cell Receptor beta
Genetic Predisposition to Disease
HLA-DQ Antigens / genetics
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
HLA-DR Antigens / genetics
HLA-DR4 Antigen / genetics
HLA-DRB1 Chains
Humans
Lymphocyte Activation
Macrophages / immunology
Male
Middle Aged
Myocarditis / etiology
Myocarditis / immunology*
Myocarditis / virology
Myocardium / immunology*
Myocardium / metabolism
RNA, Messenger / analysis
Receptors, Antigen, T-Cell, alpha-beta / analysis*
T-Lymphocyte Subsets / immunology*
Vero Cells / virology

Substances

Complementarity Determining Regions
Cytokines
DNA, Viral
HLA-DQ Antigens
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
HLA-DQA1 antigen
HLA-DQB1 antigen
HLA-DR Antigens
HLA-DR4 Antigen
HLA-DRB1 Chains
RNA, Messenger
Receptors, Antigen, T-Cell, alpha-beta