title: Increased frequency of follicular helper T cells in mice viral myocarditis is relevant with anti-ANT antoantibody.
abstract: BACKGROUND
  Recently, a new subset of CD4(+)T helper cell termed Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, has been reported to participate in some certain autoimmune diseases. But whether Tfh cells are involved in the pathogenesis of VMC remains unclear.
  
  
  METHODS
  Male BALB/c mice were intraperitoneally (i.p) infected with CVB3 to establish VMC models. Control mice were treated with phosphate-buffered saline i.p. On 0, 1, 2, 3, 4, 6 weeks post injection, frequencies of splenic Tfh cells were determined by flow cytometric analysis, productions of IL-21 and anti-adenine nucleotide translocator(ANT) autoantibody were detected by enzyme-linked immunosorbent assay. To further investigate the effects of Tfh cells, VMC mice were treated with Anti-IL-21 neutralizing antibody. Heart pathology was examined histologically, the frequencies of Tfh cells and the expressions of anti-ANT autoantibody were investigated after anti-IL-21 intervention. Spearman analysis was used to evaluate the relationship between the frequencies of Tfh cells and IL-21 levels with anti-ANT autoantibody.
  
  
  RESULTS
  The percentage of Tfh cells significantly increased in VMC mice from 1 W to 6 W, the serum level of IL-21 and ANT autoantibody were also significantly increased in VMC mice. Neutralization of IL-21 with anti-IL-21 can ameliorate the myocardium inflammation, decrease Tfh cells and ANT autoantibody after IL-21 antibody intervention compared with those of the control (P < 0.05). Both of the frequencies of Tfh cells and IL-21 levels were positively correlated with anti-ANT antibody levels (R = 0.758, P < 0.05; R = 0.88, P < 0.01, respectively).
  
  
  CONCLUSIONS
  Those results suggest that Tfh cells and IL-21 might involve in the pathogenesis of VMC and play an important role in anti-ANT autoantibody production. Targeting the Tfh cell and IL-21 may be a new therapeutic target for the treatment of CVB3-induced VMC.
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Guangxi Medical University, Liu-Shi Road 1, 545005, Liuzhou, China. lxy_xiaohu@126.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Guangxi Medical University, Liu-Shi Road 1, 545005, Liuzhou, China. 13507725632@139.com.
authors.forename: Wen-hong
authors.initials: WH
authors.lastname: Mo
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Guangxi Medical University, Liu-Shi Road 1, 545005, Liuzhou, China. 13471201458@139.com.
authors.forename: Bao-ping
authors.initials: BP
authors.lastname: Tan
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Guangxi Medical University, Liu-Shi Road 1, 545005, Liuzhou, China. 583416129@qq.com.
authors.forename: Xiao-mou
authors.initials: XM
authors.lastname: Wei
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Guangxi Medical University, Liu-Shi Road 1, 545005, Liuzhou, China. whccu059@sina.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007378:Interleukins / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000473:pathology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D033741:Adenine Nucleotide Translocator 1; D001323:Autoantibodies; D007378:Interleukins; D000098546:Interleukin-21