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http://dx.doi.org/10.5352/JLS.2006.16.6.904

The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity  

Nam, Byung-Hyouk (Dong-A University Medical Science Research Center, Clinical Research Center)
Jo, Wool-Soon (Dong-A University Medical Science Research Center, Clinical Research Center)
Lee, Ki-Won (Dong-A University Medical Science Research Center, Clinical Research Center)
Oh, Su-Jung (Dong-A University Medical Science Research Center, Clinical Research Center)
Kang, Eun-Young (Dong-A University Medical Science Research Center, Clinical Research Center)
Choi, Yu-Jin (Dong-A University Medical Science Research Center, Clinical Research Center)
Do, Eun-Ju (Dong-A University Medical Science Research Center, Clinical Research Center)
Hong, Sook-Hee (Dong-A University Medical Science Research Center, Clinical Research Center)
Lim, Young-Jin (Dong-A University Medical Science Research Center, Clinical Research Center)
Kim, Ki-Uk (Department of Neurosurgery, College of Medicine Dong-A University)
Jeong, Min-Ho (Dong-A University Medical Science Research Center, Clinical Research Center)
Publication Information
Journal of Life Science / v.16, no.6, 2006 , pp. 904-910 More about this Journal
Abstract
Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.
Keywords
Dendritic cell; cytotoxic T lymphocyte; ovalbumin; tumor immunity;
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