title: Immunological tolerance of human hepatocyte xenograft induced by adenovirus vector-mediated CTLA4Ig gene transfer.
abstract: BACKGROUND
  Systemic administration of CTLA4Ig has been applied in inducing immunological tolerance of hepatocyte implants, but has potential for systemic immune inhibition. This study was designed to induce hepatocyte immunological tolerance by locally expressing CTLA4Ig in an attempt to improve the effectiveness of cell transplantation.
  
  
  METHODS
  A normal human liver cell line (L02) was transfected with adenovirus vector containing the CTLA4Ig gene (Ad-CTLA4Ig-EGFP) in vitro, and the expression of CTLA4Ig by transfected cells was assessed by fluorescent imaging and immunocytochemical staining. Transfected cells then were injected into the spleen of Sprague-Dawley rats, the survival of cells was determined by immunohistochemistry, and the immune status was examined through CD4+ and CD69+ T cell-counts and ELISA detection of IL-2 in peripheral blood.
  
  
  RESULTS
  L02 cells expressed CTLA4Ig in the cytoplasm for >4 weeks. Surviving L02 cells were observed in the experimental group at 3 and 4 weeks post-transplantation, while none was detected in the control group. Furthermore, the percentages of CD4+ and CD4+CD69+ T cells in the CTLA4-transfected group were 24.5% and 45.1%, markedly lower than those in the control group at 4 weeks post-transplantation (P<0.01). Furthermore, the IL-2 level was also lower in the CTLA4-transfected group than in the control group.
  
  
  CONCLUSIONS
  Adenovirus-mediated CTLA4Ig gene transfer into human hepatocytes has the potential to become an effective method of inducing immunological tolerance in hepatocyte transplantation.
authors.affiliation: Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yao-Kai
authors.initials: YK
authors.lastname: Chen
authors.forename: Xiao-Cong
authors.initials: XC
authors.lastname: Liu
authors.forename: Jun-Gang
authors.initials: JG
authors.lastname: Li
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wang
mesh_terms: D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods* / Q000473:pathology; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000276:immunology* / Q000637:transplantation*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D018796:Immunoconjugates / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous; D000099192:CD69 Antigens
chemical_list: D000069594:Abatacept; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D018796:Immunoconjugates; D007376:Interleukin-2; D037181:Lectins, C-Type; D000099192:CD69 Antigens