title: Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells.
abstract: CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV) function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th) cells among the CD4+Foxp3- T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.
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 430000, China; Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zeng
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 430000, China.
authors.forename: Kunwu
authors.initials: K
authors.lastname: Yu
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 430000, China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.affiliation: The Fourth Hospital of Wuhan, Wuhan 430000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000276:immunology*
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2