Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.
DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany.
Sci Rep. 2017 Nov 22;7(1):15998. doi: 10.1038/s41598-017-16147-1.
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 Th and Th 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.
我们研究了在压力负荷增加（通过横主动脉缩窄（TAC）引起）的情况下，针对心肌细胞中抗原具有特异性的 CD4-T 细胞是否会促进从心肌肥厚向心力衰竭的进展。在 CD4-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 小鼠进行杂交。尽管其 OVA 特异性 CD4-T 细胞没有无反应性，但产生的 cMy-mOVA-OT-II 小鼠并未显示自发自身免疫的迹象。与 cMy-mOVA 小鼠相比，在 TAC 后，cMy-mOVA-OT-II 小鼠向心力衰竭的进展明显加快。在 cMy-mOVA-OT-II 小鼠中，TAC 后并未诱导针对 OVA 的特异性抗体，但与 TAC 处理的 cMy-mOVA 小鼠相比，其心肌中有更多的 CD3 T 细胞浸润。全身性地，在 TAC 后，cMy-mOVA-OT-II 小鼠中具有 Th 和 Th 细胞因子表型的活化 CD4-T 细胞的比例增加。因此，针对心肌细胞中抗原的辅助性 T 细胞可以直接促进心力衰竭的进展，而与自身抗体无关。
