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Medientyp:
E-Artikel
Titel:
T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure
Erschienen:
Springer Science and Business Media LLC, 2017
Erschienen in:
Scientific Reports, 7 (2017) 1
Sprache:
Englisch
DOI:
10.1038/s41598-017-16147-1
ISSN:
2045-2322
Entstehung:
Anmerkungen:
Beschreibung:
AbstractWe 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 Th1and Th17cytokine 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.