title: Upregulation of CD4+CD25+ T lymphocyte by adenovirus-mediated gene transfer of CTLA4Ig fusion protein in experimental autoimmune myocarditis.
abstract: OBJECTIVE
  To explore the effects of adenovirus vector-mediated gene transfer of CTLA4Ig fusion protein on CD4+CD25+ T cells in experimental autoimmune myocarditis (EAM).
  
  
  METHODS
  EAM was induced by porcine cardiac myosin as previously described. Adenovirus vector-mediated CTLA4Ig gene was administrated intravenously in EAM rats on days 1, 4 and 7, with EGFP as control. On day 21, myocardium histopathology was examined and CD4+CD25+ T cells were isolated. Proliferation and suppression assays were used to evaluate the suppressive capacity of CD4+CD25+ T cells in vitro. Relative mRNA level of Foxp3 and TGF-beta was determined by quantitative real-time RT-PCR; expression of CTLA-4, B7-1 and B7-2 protein was compared with Western blot in CD4+CD25+ Tregs.
  
  
  RESULTS
  Severe inflammatory lesions were observed in the hearts of EGFP-treated EAM rats and the untreated ones, while Ad-CMV-CTLA4Ig alleviated the myocarditis histologically. Adenovirus vector-mediated CTLA4Ig gene transfer up-regulated the proportion of CD4+CD25+ Tregs significantly. T cell proliferation was greatly inhibited in the CTLA4Ig group compared with the untreated and EGFP-treated groups in vitro. CTLA-4 and B7-2 proteins were down-regulated in the CTLA4Ig group, Foxp3 and TGF-beta mRNA was up-regulated significantly by CTLA4Ig treatment.
  
  
  CONCLUSIONS
  Adenovirus vector-mediated CTLA4Ig gene transfer alleviated inflammation in EAM, one of the potential mechanisms is up-regulation of CD4+CD25+ Tregs.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Heilongjiang 150001, People's Republic of China. doctor_liuwei@yahoo.com.cn
authors.forename: Liu
authors.initials: L
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Wei-Min
authors.forename: Gao
authors.initials: G
authors.lastname: Cheng
authors.forename: Zhou
authors.initials: Z
authors.lastname: Bao-Guo
mesh_terms: D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D015704:CD4 Antigens / Q000097:blood / Q000276:immunology; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D009205:Myocarditis / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018796:Immunoconjugates; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D000069594:Abatacept