T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure

2017 | journal article; research paper

Jump to: Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure​
Gröschel, C. ; Sasse, A. ; Röhrborn, C. ; Monecke, S. ; Didié, M. ; Elsner, L.   & Kruse, V.  et al.​ (2017) 
Scientific Reports7(1) art. 15998​.​ DOI: https://doi.org/10.1038/s41598-017-16147-1 

Documents & Media

s41598-017-16147-1.pdf12.02 MBAdobe PDFdocument.pdf12.26 MBAdobe PDF

License

Published Version

Attribution 4.0 CC BY 4.0

Details

Authors
Gröschel, Carina ; Sasse, André ; Röhrborn, Charlotte ; Monecke, Sebastian ; Didié, Michael ; Elsner, Leslie ; Kruse, Vanessa ; Bunt, Gertrude; Lichtman, Andrew H.; Toischer, Karl ; Zimmermann, Wolfram-Hubertus ; Dressel, Ralf ; Hasenfuß, Gerd 
Abstract
We investigated whether CD4+-T cells with specificity for an antigen in cardiomyocytes promote the progression from hypertrophy to heart failure in mice with increased pressure load due to transverse aortic constriction (TAC). OT-II mice expressing a transgenic T cell receptor (TCR) with specificity for ovalbumin (OVA) on CD4+-T cells and cMy-mOVA mice expressing OVA on cardiomyocytes were crossed. The resulting cMy-mOVA-OT-II mice did not display signs of spontaneous autoimmunity despite the fact that their OVA-specific CD4+-T cells were not anergic. After TAC, progression to heart failure was significantly accelerated in cMy-mOVA-OT-II compared to cMy-mOVA mice. No OVA-specific antibodies were induced in response to TAC in cMy-mOVA-OT-II mice, yet more CD3+ T cells infiltrated their myocardium when compared with TAC-operated cMy-mOVA mice. Systemically, the proportion of activated CD4+-T cells with a Th1 and Th17 cytokine profile was increased in cMy-mOVA-OT-II mice after TAC. Thus, T helper cells with specificity for an antigen in cardiomyocytes can directly promote the progression of heart failure in response to pressure overload independently of autoantibodies.
Issue Date
2017
Journal
Scientific Reports 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur 
SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien 
SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation 
SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle 
Working Group
RG Dressel 
RG Hasenfuß (Transition zur Herzinsuffizienz) 
RG Toischer (Kardiales Remodeling) 
RG Zimmermann (Engineered Human Myocardium) 
ISSN
2045-2322
Language
English
Sponsor
Open-Access-Publikationsfonds 2017

Reference

Citations


Social Media