Basic Research in Cardiology

, 107:232

Regulatory T cells ameliorate cardiac remodeling after myocardial infarction

  • Ting-Ting Tang
  • Jing Yuan
  • Zheng-Feng Zhu
  • Wen-Cai Zhang
  • Hong Xiao
  • Ni Xia
  • Xin-Xin Yan
  • Shao-Fang Nie
  • Juan Liu
  • Su-Feng Zhou
  • Jing-Jing Li
  • Rui Yao
  • Meng-Yang Liao
  • Xin Tu
  • Yu-Hua Liao
  • Xiang Cheng
Original Contribution

DOI: 10.1007/s00395-011-0232-6

Cite this article as:
Tang, TT., Yuan, J., Zhu, ZF. et al. Basic Res Cardiol (2012) 107: 232. doi:10.1007/s00395-011-0232-6

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.

Keywords

Regulatory T cells Myocardial infarction Cardiac remodeling CD28 superagonists 

Supplementary material

395_2011_232_MOESM1_ESM.pdf (114 kb)
Supplementary material 1 (PDF 113 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ting-Ting Tang
    • 1
  • Jing Yuan
    • 1
  • Zheng-Feng Zhu
    • 1
  • Wen-Cai Zhang
    • 1
  • Hong Xiao
    • 2
  • Ni Xia
    • 1
  • Xin-Xin Yan
    • 1
  • Shao-Fang Nie
    • 1
  • Juan Liu
    • 1
  • Su-Feng Zhou
    • 1
  • Jing-Jing Li
    • 1
  • Rui Yao
    • 1
  • Meng-Yang Liao
    • 1
  • Xin Tu
    • 3
  • Yu-Hua Liao
    • 1
  • Xiang Cheng
    • 1
  1. 1.Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of EducationInstitute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina
  2. 2.The NO1 Hospital of WuhanWuhanChina
  3. 3.Key Laboratory of Molecular Biophysics of the Ministry of EducationCardio-X Institute, College of Life Science and Technology and Center of Human Genome Research, Huazhong University of Science and TechnologyWuhanChina

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