Coxsackievirus B3 Infection Leads to the Generation of Cardiac Myosin Heavy Chain-α-Reactive CD4 T Cells in A/J Mice

Authors

Arunakumar Gangaplara, University of Nebraska - Lincoln
Chandirasegaran Massilamany, University of Nebraska-LincolnFollow
Deborah M. Brown, University of Nebraska - LincolnFollow
Gustavo A. Delhon, University of Nebraska - LincolnFollow
Asit K. Pattnaik, University of Nebraska - LincolnFollow
Nora Chapman, Johns Hopkins Medical Institutions
Noel Rose, Johns Hopkins Medical Institutions
David J. Steffen, University of Nebraska - LincolnFollow
Jay Reddy, University of Nebraska - LincolnFollow

Document Type

Article

Date of this Version

2012

Citation

Clinical Immunology (2012) 144: 237-249. DOI: 10.1016/j/clim.2012.07.003.

Comments

Copyright 2012, Elsevier. Used by permission.

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.