Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-α-reactive CD4 T cells in A/J mice

Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David Steffen, Jay Reddy

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA k dextramers for cardiac myosin heavy chain (Myhc)-α 334-352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334-352 and IA k dextramer staining. We also detected Myhc-α 334-352 dextramer + cells in the hearts of CVB3-infected mice. The autoreactive T cell repertoire derived from infected mice contained a high frequency of interleukin-17-producing cells capable of inducing myocarditis in naïve recipients. The data suggest that CVB3, a bona fide pathogen of cardiovascular system that primarily infects the heart can lead to the secondary generation of autoreactive T cells and contribute to cardiac pathology.

Original languageEnglish (US)
Pages (from-to)237-249
Number of pages13
JournalClinical Immunology
Volume144
Issue number3
DOIs
StatePublished - Sep 2012

Keywords

  • Autoimmunity;
  • Autoreactive T cells;
  • Cardiac myosin heavy chain-α;
  • Coxsackievirus B3;
  • MHC class II dextramers
  • Myocarditis;

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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