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Two-step maturation of immature DCs with proinflammatory cytokine cocktail and poly(I:C) enhances migratory and T cell stimulatory capacity

 Hyung Jin Kim  ;  Hyun-Ok Kim  ;  Kyungwon Lee  ;  Eun Jung Baek  ;  Han-Soo Kim 
 VACCINE, Vol.28(16) : 2877-2886, 2010 
Journal Title
Issue Date
Adjuvants, Immunologic/pharmacology* ; Cell Movement ; Cells, Cultured ; Cytokines/pharmacology* ; Dendritic Cells/drug effects* ; Dendritic Cells/immunology* ; Flow Cytometry ; Human Experimentation ; Humans ; Poly I-C/pharmacology* ; T-Lymphocytes/immunology*
Dendritic cells ; Poly(I:C) ; Cytokine cocktail ; Sequential stimulation ; STAT3 phosphorylation
Effective induction of cell-mediated immune responses strongly depends on the ability of dendritic cells (DCs) to produce Th1-polarizing cytokines, migrate to lymph nodes and stimulate T cells through antigen-presenting complex and costimulatory molecules. While various protocols for optimizing DC maturation with single or multiple stimuli mimicking infections or inflammatory milieu have been proposed for the generation of DCs with features desired for clinical application, stepwise maturation of DCs by these multiple stimuli has not been systemically assessed. Among the combinations of several immune-modulating factors with known effects on DC maturation, we found that stepwise DC maturation with cytokine cocktail (TNF-alpha+IL-6+IL-1 beta+PGE(2)) followed by poly(I:C) stimulation enhanced the production of IL-12 with strong allostimulatory capacity. While there were no significant differences between DC matured by simultaneous or sequential activation by cytokine cocktail and poly(I:C) in expression of markers and costimulatory molecules of mature DCs, the delivery of inflammatory signal prior to poly(I:C) results in sustained interleukin-12 expression with reduced IL-10 than DC matured by simultaneous stimulation. This sequential stimulation significantly increased migratory capacity in response to CCL21 and CXCL12 compared to DC matured with cytokine cocktail. Furthermore, these DCs retained their responsiveness to CD40L stimulation in secondary IL-12 production and efficiently generated autologous antigen-specific effector T cells as evidenced by ELISPOT assay. Thus, we propose a novel DC maturation protocol in which stimulation of DCs with cytokine cocktail and subsequently with poly(I:C) generates DCs with a high migratory capacity with a preferential Th1 inducing capacity
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Han Soo(김한수)
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Kim, Hyung Jin(김형진)
Baek, Eun Jung(백은정)
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