生物
CD80
CD40
CD14型
树突状细胞
细胞生物学
细胞分化
肿瘤坏死因子α
免疫系统
免疫学
干扰素
体外
细胞毒性T细胞
生物化学
基因
作者
Bradford L. McRae,Toshiaki Nagai,Roshanak Tolouei Semnani,Jean Maguire van Seventer,Gijs A. van Seventer
出处
期刊:Blood
[American Society of Hematology]
日期:2000-07-01
卷期号:96 (1): 210-217
被引量:96
标识
DOI:10.1182/blood.v96.1.210
摘要
Abstract Dendritic cell (DC) precursors and immature DC reside in epithelium where they encounter pathogens and cytokines, which stimulate their differentiation. We hypothesized that type-I interferons (IFN- and -β), cytokines that are produced early in the innate immune response against viruses and some bacteria, may influence DC differentiation and function. To examine this possibility, we used an in vitro model of DC differentiation in which initial culture of human CD14+monocytes with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 generates immature DC, and subsequent culture with tumor necrosis factor (TNF)- drives the final development into mature DC. We found in this model that IFN-/β, added from the initiation of the culture on, significantly reduced the survival and altered the morphology and differentiation of DC. TNF-–dependent maturation of IFN-β–treated immature DC led to cells with reduced expression of CD1a, CD40, CD54, and CD80 when compared with mature DC controls. IFN-/β–treated DC further had a reduced capacity to induce naive Th-cell proliferation through allostimulation or anti-CD3 monoclonal antibody stimulation. In addition, IFN-/β–treated DC secreted less IL-12 upon stimulation with Staphylococcus aureus Cowan strain or with CD4+ T cells, and this decrease correlated directly with their inability to support CD4+ T-cell secretion of IFN-γ, even though T-cell lymphotoxin production was unaffected. These findings indicate that type-I IFNs can influence the generation of acquired immune responses by modifying T-helper cell differentiation through the regulation of DC differentiation and function.
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