title: Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-α-reactive CD4 T cells in A/J mice.
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.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, USA.
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Brown
authors.forename: Gustavo
authors.initials: G
authors.lastname: Delhon
authors.forename: Asit K
authors.initials: AK
authors.lastname: Pattnaik
authors.forename: Nora
authors.initials: N
authors.lastname: Chapman
authors.forename: Noel
authors.initials: N
authors.lastname: Rose
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D024722:Cardiac Myosins / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000473:pathology; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000276:immunology*; D006321:Heart / Q000821:virology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000821:virology; D018995:Myosin Heavy Chains / Q000276:immunology*; D014709:Vero Cells
chemical_list: D020381:Interleukin-17; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains