Enhancement of antigen presenting function of dendritic cells by IL-2 gene modification and its mechanism.
- Author:
Lifei SUN
1
;
Jiang LIU
;
Xuetao CAO
;
Minghui ZHANG
;
Yihong ZHOU
;
Bin LIU
;
Hua SHI
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Antigen Presentation; immunology; B7-1 Antigen; genetics; metabolism; Dendritic Cells; cytology; immunology; Female; Interleukin-12; secretion; Interleukin-2; genetics; Lymphocyte Activation; genetics; immunology; Mice; Mice, Inbred C57BL; Recombination, Genetic; genetics; immunology; T-Lymphocytes, Cytotoxic; cytology; immunology
- From: Chinese Journal of Hematology 2002;23(5):247-250
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of IL-2 gene modification enhancement of the antigen-presenting function of the mouse bone marrow derived dendritic cells and on the activation of CTL induced by MHC class I molecule restricted antigen peptides as well as the related immunological mechanisms.
METHODSDCs were prepared from mouse bone marrow and modified by recombinant IL-2 adenovirus (DC-IL-2). The IL-12 and IFN-gamma levels in culture supernatant of DC and CTL were examined by ELISA, the expression of costimulatory molecules and fluorescent intensity of endocytosis of OVA-FITC in DC by FACS, the capacity of presenting 3LL cell tumor antigen by (3)H-TdR incorporation method, the MHC class I-restricted tumor-antigen-peptide Mut1 of 3LL cells pulsed DC-IL-2 to induce CTL cytotoxicity by (51)Cr 4-hr releasing assay.
RESULTSAfter IL-2 gene modification, DC-IL-2 could produce high level of IL-12 [(78.4 +/- 6.6) pg.(1 x 10(6) cells)(-1).ml(-1)]. The expression of costimulatory molecules on DC-IL-2 was increased, the fluorescent intensity of DC captured OVA-FITC was enhanced, and the proliferation of allo-T cells from 3LL bearing mouse pulsed with Mut1 was also enhanced. Mut1 antigen peptide pulsed DC-IL-2 could induce more potent antigen-specific CTL cytotoxicity and excrete high concentration of IFN-gamma [(1 168 +/- 58.4) pg/ml] in vivo.
CONCLUSIONIL-2 gene modification of DC can activate second signal for DC presenting antigen, and enhance the function for capturing and presenting tumor antigen. DC-IL-2 pulsed with MHC class I restricted tumor-antigen-peptide can induce specific anti-tumor immune response more effectively. Owing to IL-2 gene modification, the functions of IL-12 excretion and T cell activation of DC were promoted, so that the capacity of CTL excreting IFN-gamma was enhanced, which are relevant to the immune mechanism.