Activation of CD4+ T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice
Activation of CD4+ T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice
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DOI：
10.1161/circulationaha.111.044164
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发表时间：
2012-04-03
期刊：
影响因子：
37.8
通讯作者：
Frantz, Stefan
中科院分区：
文献类型：
--
作者：
Hofmann, Ulrich;Beyersdorf, Niklas;Frantz, Stefan
背景-获得性免疫，特别是CD 4（+）T辅助细胞在心肌梗死（MI）后伤口愈合和重塑中的作用尚未得到系统研究。因此，我们研究了CD 4（+）T细胞是否被激活，并影响伤口愈合后，实验性MI mice.Methods和Results-When我们比较了假与MI野生型（WT）小鼠，T细胞受体依赖性激活的传统Foxp 3（-）和调节Foxp 3（+）CD 4（+）T细胞可以证明在心脏引流淋巴结MI后的第一周内。同时，我们发现CD 4（+）T细胞在梗死心肌中浸润。为了研究CD 4（+）T细胞在伤口愈合和重塑中的作用，研究了CD 4（+）T细胞缺陷小鼠（CD 4敲除[KO]，MHCII Delta/Delta）和识别无关卵清蛋白衍生肽的T细胞受体转基因OT-II小鼠。MI后56天的连续超声心动图显示，与WT小鼠相比，CD 4 KO小鼠的左心室扩张增加。在梗死心肌内，CD 4 KO小鼠显示出较高的白细胞和促炎单核细胞总数（18.3 +/- 3.0 × 10（4）/mg WT对75.7 +/- 17.0 × 10（4）/mg CD 4 KO，P < 0.05）。与WT小鼠相比，MHCII Delta/Delta和OT-II小鼠显示出显著更高的死亡率（21%WT对48% OT-II，P < 0.05，以及WT 22%对52%MHCII Delta/Delta，P < 0.05）和心肌破裂率。在CD 4 KO和MHCII Delta/Delta小鼠以及OT-II小鼠中，梗死区的胶原基质形成受到严重干扰。结论-本研究提供了第一个证据，即MI后CD 4（+）T细胞被激活，可能是由心脏自身抗原的识别驱动，并促进心肌的伤口愈合。（循环。2012; 125：1652-1663）。
Background-The role of adaptive immunity, especially CD4(+) T-helper cells, has not yet been systematically investigated in wound healing and remodeling after myocardial infarction (MI). Therefore, we studied whether CD4(+) T cells become activated and influence wound healing after experimental MI in mice.Methods and Results-When we compared sham versus MI in wild-type (WT) mice, T-cell receptor-dependent activation of both conventional Foxp3(-) and regulatory Foxp3(+) CD4(+) T cells could be demonstrated in heart-draining lymph nodes within the first week after MI. Concomitantly, we found infiltration of CD4(+) T cells in infarcted myocardium. To study the role of CD4(+) T cells in wound healing and remodeling, CD4(+) T-cell-deficient mice (CD4 knockout [KO], MHCII Delta/Delta) and T-cell receptor-transgenic OT-II mice recognizing an irrelevant ovalbumin-derived peptide were studied. Serial echocardiography up to day 56 after MI revealed increased left ventricular dilation in CD4 KO compared with WT mice. Within the infarcted myocardium, CD4 KO mice displayed higher total numbers of leukocytes and proinflammatory monocytes (18.3 +/- 3.0 10(4)/mg WT versus 75.7 +/- 17.0 10(4)/mg CD4 KO, P < 0.05). MHCII Delta/Delta and OT-II mice displayed significantly greater mortality (21% WT versus 48% OT-II, P < 0.05, and WT 22% versus 52% MHCII Delta/Delta, P < 0.05) and myocardial rupture rates than WT mice. Collagen matrix formation in the infarct zone was severely disturbed in CD4 KO and MHCII Delta/Delta mice, as well as in OT-II mice.Conclusions-The present study provides the first evidence that CD4(+) T cells become activated after MI, presumably driven by recognition of cardiac autoantigens, and facilitate wound healing of the myocardium. (Circulation. 2012; 125: 1652-1663.)