Gröschel, CarinaSasse, AndréRöhrborn, CharlotteMonecke, SebastianDidié, MichaelElsner, LeslieKruse, VanessaBunt, GertrudeLichtman, AndrewToischer, KarlZimmermann, Wolfram-HubertusHasenfuß, GerdDressel, Ralf2017-12-062017Gröschel, 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.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493129We 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.en-USJournal Article2017-12-0610.1038/s41598-017-16147-1