Matsumoto Kazuaki, Ogawa Masahito, Suzuki Jun-ichi, Hirata Yasunobu, Nagai Ryozo, Isobe Mitsuaki
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Int Heart J. 2011;52(6):382-7. doi: 10.1536/ihj.52.382.
Downregulation of CD4+CD25+ regulatory T lymphocytes (Treg) has been found in local atherosclerotic lesions and in patients with myocardial infarction (MI). However, the roles of Treg in MI and the following inflammatory response have not yet been well elucidated. Therefore, we hypothesized that adoptive transfer of Treg could attenuate the postinfarction inflammatory response protecting from adverse remodeling, and we attempted to elucidate the mechanism of delayed heart failure after MI. To clarify the role of Treg in MI, we used a murine MI model and administered a single intravenous injection of Treg (1 × 10(5)) (treatment, n = 6) or saline (control, n = 7) and sacrificed the mice on day 14. Echocardiograms revealed that Treg improved LV contraction after MI. Histopathology also showed that Treg negated MI-induced LV remodeling. RT-PCR demonstrated that the mRNA levels of IFN-gamma in hearts were lower and Foxp3 in spleens were higher in the treatment group than in the control group. We observed that adoptive Treg transfer could attenuate MI-induced cardiac remodeling through the IFN-gamma and Foxp3 alteration.
在局部动脉粥样硬化病变以及心肌梗死（MI）患者中，已发现CD4+CD25+调节性T淋巴细胞（Treg）数量下调。然而，Treg在心肌梗死及后续炎症反应中的作用尚未完全阐明。因此，我们推测过继性转移Treg可减轻梗死后的炎症反应，预防不良重塑，并且我们试图阐明心肌梗死后延迟性心力衰竭的机制。为明确Treg在心肌梗死中的作用，我们使用小鼠心肌梗死模型，单次静脉注射Treg（1×10⁵）（治疗组，n = 6）或生理盐水（对照组，n = 7），并于第14天处死小鼠。超声心动图显示，Treg改善了心肌梗死后左心室收缩功能。组织病理学也表明，Treg抑制了心肌梗死诱导的左心室重塑。逆转录聚合酶链反应（RT-PCR）表明，治疗组心脏中γ干扰素（IFN-γ）的mRNA水平低于对照组，脾脏中叉头框蛋白3（Foxp3）的mRNA水平高于对照组。我们观察到，过继性转移Treg可通过改变IFN-γ和Foxp3来减轻心肌梗死诱导的心脏重塑。
