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 language | English (US) |
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Pages (from-to) | 237-249 |
Number of pages | 13 |
Journal | Clinical Immunology |
Volume | 144 |
Issue number | 3 |
DOIs | |
State | Published - 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