title: Dendritic cells modified with 6Ckine/IFNgamma fusion gene induce specific cytotoxic T lymphocytes in vitro.
abstract: OBJECTIVE
  [corrected] Dendritic cells play an important role in initiation and regulation of immune responses. Previous studies demonstrated that intratumoral administration of 6Ckine-modified DCs enhanced local and systemic antitumor effects. Herein we report the investigation of the specific CTL responses elicited by adenoviral 6Ckine/IFNgamma fusion gene-modified DCs in vitro.
  
  
  METHODS
  Human monocyte-derived DCs were modified with an adenoviral vector encoding 6Ckine/IFNgamma fusion protein (Ad-6Ckine/IFNgamma), and then investigated the effect of 6Ckine/IFNgamma fusion protein on the maturation, cytokine and chemokine secretion of DCs, and their activities of recruiting and activating T cells in vitro were investigated.
  
  
  RESULTS
  6Ckine/IFNgamma fusion protein induced DC maturation characterized with the upregulation of CD83 and CCR7. And it up-regulated the expression of RANTES and IL-12p70, down-regulated that of IL-10 in DCs. Additionally, 6Ckine/IFNgamma markedly increased DC's recruiting ability for naive T cells, benefiting from the enhanced expression of chemokines 6Ckine and RANTES in DCs. Fusion gene-modified DCs significantly promoted the proliferation of autologous T cells, induced Th1 differentiation by upregulating the expression of IL-2 and T-bet in T cells, and increased specific cytotoxicity of CTLs against specific tumor cells, HepG2 or LoVo cells, respectively.
  
  
  CONCLUSIONS
  Combining the effects of 6Ckine and IFNgamma, Ad-6Ckine/IFNgamma modified DCs induced enhanced CTL responses in vitro, which indicated that Ad-6Ckine/IFNgamma modified DCs might be used as an adjuvant to trigger an effective antitumor immune response.
authors.affiliation: Department of General Surgery, Chengdu Army General Hospital, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xue
authors.forename: Ran-Yi
authors.initials: RY
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Liang
authors.forename: Jiang-Xue
authors.initials: JX
authors.lastname: Wu
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Fu-Zhou
authors.initials: FZ
authors.lastname: Tian
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors; D045744:Cell Line, Tumor; D054421:Chemokine CCL21; D019742:Chemokines, CC; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; C515478:CCL21 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma