Interleukin-10 does not affect phagocytosis of particulate antigen by bonemarrow-derived dendritic cells but does impair antigen presentation

Interleukin-10 does not affect phagocytosis of particulate antigen by bonemarrow-derived dendritic cells but does impair antigen presentation
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DOI:
10.1046/j.1365-2567.2000.00018.x
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发表时间:
2000-04-01
期刊:
影响因子:
6.4
通讯作者:
Baird, M
Baird, M
中科院分区:
医学2区
文献类型:
--
作者:
Faulkner, L;Buchan, G;Baird, M

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树突状细胞(DC)是免疫应答的重要启动者,因此了解控制抗原获得和呈递的因素对这些细胞在疫苗和其他形式的免疫疗法中的使用具有重要意义。我们研究了影响未成熟骨髓来源的DC(BMDC)吞噬功能的因素以及白细胞介素-10(IL-10)对该过程的影响。使用两种大小的荧光颗粒和表达绿色荧光蛋白(rBCG)的重组卡介苗作为颗粒抗原。发现摄取抗原的细胞百分比取决于颗粒的大小和剂量以及暴露于它们的时间长度。BMDC暴露于不同浓度的IL-10不同时期的抗原摄取没有表现出明显的变化。然而,如果用IL-10和rBCG处理的BMDC然后暴露于第二剂量的颗粒抗原,则与未用IL-10处理的BMDC相比,摄取增加。经IL-10预处理后,BMDC吞噬rBCG或惰性磁珠后,其主要组织相容性复合物Ⅱ类分子CD 80、CD 86和CD 11 c的表达均受到抑制。相反,CD 25的表达增加。已经摄取BCG或纯化蛋白衍生物(PPD)的BMDC能够刺激致敏的T细胞增殖,但是如果BMDC在暴露于抗原之前与IL-10一起培养,则这被严重抑制。这项工作表明,虽然IL-10不影响BMDC的吞噬能力,但它确实抑制细胞的成熟,从而抑制T细胞活化。
Dendritic cells (DC) are important initiators of an immune response so understanding the factors controlling antigen acquisition and presentation has important consequences for the use of these cells in vaccines and other forms of immunotherapy. We investigated the factors that influence phagocytosis by immature bone marrow-derived DC (BMDC) and the effect of interleukin-10 (IL-10) on this process. Two sizes of fluorescent particles and recombinant bacillus Calmette-Guerin expressing the green fluorescent protein (rBCG) were used as particulate antigens. The percentage of cells taking up the antigen was found to be dependent on the size and dose of the particles, and the length of exposure to them. BMDC exposed to IL-10 at various concentrations for different periods exhibited no distinguishable change in antigen uptake. However, if BMDC treated with IL-10 and rBCG were then exposed to a second dose of particulate antigen, uptake was increased compared with those BMDC not treated with IL-10. The expression of major histocompatibility complex class II, CD80, CD86 and CD11c by BMDC after phagocytosing rBCG or inert beads, was inhibited when the BMDC were pretreated with IL-10. In contrast, the expression of CD25 was increased. BMDC that had taken up BCG or purified protein derivative (PPD) were able to stimulate primed T-cell proliferation but this was severely inhibited if the BMDC were cultured with IL-10 before exposure to the antigen. This work suggests that although IL-10 does not affect the phagocytic capacity of BMDC, it does inhibit maturation of the cells and consequently, T-cell activation.