title: Regulatory T cells ameliorate cardiac remodeling after myocardial infarction.
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.
authors.affiliation: Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Zheng-Feng
authors.initials: ZF
authors.lastname: Zhu
authors.forename: Wen-Cai
authors.initials: WC
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Ni
authors.initials: N
authors.lastname: Xia
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Yan
authors.forename: Shao-Fang
authors.initials: SF
authors.lastname: Nie
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Su-Feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Yao
authors.forename: Meng-Yang
authors.initials: MY
authors.lastname: Liao
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D020257:Ventricular Remodeling / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C568777:JJ 316; D016753:Interleukin-10