Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1beta + interferon (IFN)-gamma.
Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour- or pathogen-specific T cell responses. For adoptive immunotherapy purposes, immature DCs can be generated from adherent monocytes using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further maturation is usually achieved by incubation with tumour necrosis factor (TNF)-alpha. However, TNF-alpha-stimulated DCs produce low levels of IL-12. In this study, we compared the effects of TNF-alpha, interferon (IFN)-gamma, IL-1beta or IFN-gamma + IL-1beta on the phenotypic and functional maturation of DCs. Our results show that IFN-gamma, but not IL-1beta, augmented the surface expression of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs. However, IL-1beta, but not IFN-gamma, induced IL-12 p40 production by DCs without enhancing phenotypic maturation. When combined, IFN-gamma + IL-1beta treatment profoundly up-regulated the expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens. Furthermore, IFN-gamma + IL-1beta-treated DCs produced larger amounts of IL-12 and induced stronger T cell proliferation and IFN-gamma secretion in primary allogeneic mixed lymphocyte reaction (MLR) than did TNF-alpha-treated DCs. Our results show that IFN-gamma + IL-1beta induced human monocyte-derived DCs to differentiate into Th1-prone mature DCs.
Nakahara
T
T
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nakahara@dermatol.med.kyushu-u.ac.jp
Urabe
K
K
Fukagawa
S
S
Uchi
H
H
Inaba
K
K
Furue
M
M
Moroi
Y
Y
D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma
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