Dendritic cells modified with 6Ckine/IFNgamma fusion gene induce specific cytotoxic T lymphocytes in vitro.
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.
Xue
Gang
G
Department of General Surgery, Chengdu Army General Hospital, Chengdu, China.
Liu
Ran-Yi
RY
Li
Yan
Y
Cheng
Ying
Y
Liang
Zhi-Hui
ZH
Wu
Jiang-Xue
JX
Zeng
Mu-Sheng
MS
Tian
Fu-Zhou
FZ
Huang
Wenlin
W
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
D020533:Angiogenesis Inhibitors; C515478:CCL21 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma