T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure.
T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure.
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DOI：
10.1038/s41598-017-16147-1
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发表时间：
2017-11-22
影响因子：
4.6
通讯作者：
Dressel R
中科院分区：
文献类型：
--
作者：
Gröschel C;Sasse A;Röhrborn C;Monecke S;Didié M;Elsner L;Kruse V;Bunt G;Lichtman AH;Toischer K;Zimmermann WH;Hasenfuß G;Dressel R
我们研究了是否CD 4 +-T细胞特异性抗原的心肌细胞促进从肥大到心力衰竭的进展，由于横向主动脉缩窄（TAC）的压力负荷增加的小鼠。将在CD 4 +-T细胞上表达对卵清蛋白（OVA）具有特异性的转基因T细胞受体（TCR）的OT-II小鼠和在心肌细胞上表达OVA的cMy-mOVA小鼠杂交。所得的cMy-mOVA-OT-II小鼠没有显示自发性自身免疫的迹象，尽管它们的OVA特异性CD 4 +-T细胞不是无反应性的。TAC后，与cMy-mOVA小鼠相比，cMy-mOVA-OT-II中心力衰竭的进展显著加速。在cMy-mOVA-OT-II小鼠中，没有OVA特异性抗体被诱导响应于TAC，但与TAC操作的cMy-mOVA小鼠相比，更多的CD 3 + T细胞浸润其心肌。在系统方面，TAC后cMy-mOVA-OT-II小鼠中具有Th 1和Th 17细胞因子谱的活化CD 4 +-T细胞的比例增加。因此，对心肌细胞中的抗原具有特异性的T辅助细胞可以直接促进心力衰竭的进展，以响应压力超负荷，而不依赖于自身抗体。
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.
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影响因子：
37.8
作者：
Kvakan, Heda;Kleinewietfeld, Markus;Muller, Dominik N.
通讯作者：
Muller, Dominik N.
影响因子：
37.8
作者：
Hofmann, Ulrich;Beyersdorf, Niklas;Frantz, Stefan
通讯作者：
Frantz, Stefan
DOI：
10.1161/circheartfailure.112.000080
发表时间：
2013-05
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Divakaran VG;Evans S;Topkara VK;Diwan A;Burchfield J;Gao F;Dong J;Tzeng HP;Sivasubramanian N;Barger PM;Mann DL
通讯作者：
Mann DL
影响因子：
15.9
作者：
Lv, HuiJuan;Havari, Evis;Lipes, Myra A.
通讯作者：
Lipes, Myra A.
影响因子：
18.2
作者：
Deubner, Nikolas;Berliner, Dominik;Jahns, Roland
通讯作者：
Jahns, Roland