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Regulatory T cells ameliorate cardiac remodeling after myocardial infarction

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Abstract

Persistent inflammatory responses participate in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We hypothesized that regulatory T (Treg) cells modulate inflammatory responses, attenuate ventricular remodeling and subsequently improve cardiac function after MI. Acute MI was induced by ligation of the left anterior descending coronary artery in rats. Infiltration of Foxp3+ Treg cells was detected in the infarcted heart. Expansion of Treg cells in vivo by means of adoptive transfer as well as a CD28 superagonistic antibody (JJ316) resulted in an increased number of Foxp3+ Treg cells in the infarcted heart. Subsequently, rats with MI showed improved cardiac function following Treg cells transfer or JJ316 injection. Interstitial fibrosis, myocardial matrix metalloproteinase-2 activity and cardiac apoptosis were attenuated in the rats that received Treg cells transfer. Infiltration of neutrophils, macrophages and lymphocytes as well as expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were also significantly decreased, and the CD8+ cardiac-specific cytotoxic T lymphocyte response was inhibited. Expression of interleukin (IL)-10 in the heart, however, was increased. Additional studies in vitro indicated that Treg cells directly protect neonatal rat cardiomyocytes against LPS-induced apoptosis, and this protection depends on the cell–cell contact and IL-10 expression. Furthermore, Treg cells inhibited proinflammatory cytokines production by cardiomyocytes. These data demonstrate that Treg cells serve to protect against adverse ventricular remodeling and contribute to improve cardiac function after myocardial infarction via inhibition of inflammation and direct protection of cardiomyocytes.

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Acknowledgments

This work was supported by grants from National Basic Research Program of China (973 Program: 2012CB517805 and 2007CB512005 to YHL and XC), National Natural Science Foundation of China (No. 81170303 and 30871067 to XC; 81070106 to XT) and Program for New Century Excellent Talents in University of China (NCET-09-0380 to XC).

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Correspondence to Yu-Hua Liao or Xiang Cheng.

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T.-T. Tang and J. Yuan contributed equally to this study.

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Tang, TT., Yuan, J., Zhu, ZF. et al. Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol 107, 232 (2012). https://doi.org/10.1007/s00395-011-0232-6

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