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

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

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Title: T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure
Author: Gröschel, Carina; Sasse, André; Röhrborn, Charlotte; Monecke, Sebastian; Didié, Michael; Elsner, Leslie; Kruse, Vanessa; Bunt, Gertrude; Lichtman, Andrew H.; Toischer, Karl; Zimmermann, Wolfram-Hubertus; Hasenfuß, Gerd; Dressel, Ralf

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Citation: Gröschel, C., A. Sasse, C. Röhrborn, S. Monecke, M. Didié, L. Elsner, V. Kruse, et al. 2017. “T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure.” Scientific Reports 7 (1): 15998. doi:10.1038/s41598-017-16147-1. http://dx.doi.org/10.1038/s41598-017-16147-1.
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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.
Published Version: doi:10.1038/s41598-017-16147-1
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700082/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493129
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