Jørgensen T N, Haase C, Michelsen B K
Hagedorn Research Institute, Gentofte, Denmark.
Scand J Immunol. 2002 Nov;56(5):492-503. doi: 10.1046/j.1365-3083.2002.01166.x.
Antigen-presenting cells (APCs) are crucial for the generation of a functional immune response to pathogens. Furthermore, there is abundant evidence for their importance in primary T-cell activation, B-cell maturation and maintenance of an ongoing immune response. In the present study, we have analysed phenotypic characteristics and functionality of a p53-deficient APC cell line (JawsII) derived from mouse bone marrow culture. We show that unstimulated JawsII cells express low surface levels of major histocompatibility complex (MHC) and costimulatory molecules, both of which can be upregulated upon treatment with cytokines in vitro. Cytokine stimulation also leads to an enhanced T-cell activation capacity but has only little effect on cytokine release by the JawsII cells themselves. On the contrary, stimulation of the JawsII cells with lipopolysaccharide (LPS) leads to the production and secretion of high amounts of interleukin-1 (IL-1), IL-6 and tumour necrosis factor-alpha (TNF-alpha) but no increase in the surface levels of MHC and costimulatory molecules, and has only little effect on the T-cell activation capacity. Our data suggest that the effects observed upon treatment with cytokines or LPSs are complementary, and that both stimuli are needed for mediating a strong and efficient JawsII cell-dependent T-cell activation.
抗原呈递细胞(APC)对于针对病原体产生功能性免疫反应至关重要。此外,有大量证据表明它们在原发性T细胞活化、B细胞成熟以及维持持续免疫反应中具有重要作用。在本研究中,我们分析了源自小鼠骨髓培养的p53缺陷型APC细胞系(JawsII)的表型特征和功能。我们发现,未受刺激的JawsII细胞表达低水平的主要组织相容性复合体(MHC)和共刺激分子,在体外经细胞因子处理后,这两者均可上调。细胞因子刺激还会导致T细胞活化能力增强,但对JawsII细胞自身的细胞因子释放影响很小。相反,用脂多糖(LPS)刺激JawsII细胞会导致大量白细胞介素-1(IL-1)、IL-6和肿瘤坏死因子-α(TNF-α)的产生和分泌,但MHC和共刺激分子的表面水平没有增加,并且对T细胞活化能力影响很小。我们的数据表明,细胞因子或LPS处理后观察到的效应是互补的,并且两种刺激对于介导强烈且有效的JawsII细胞依赖性T细胞活化都是必需的。