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桦树过敏个体中单核细胞衍生树突状细胞的成熟受损与桦树特异性免疫反应相关。

Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses.

作者信息

Casas R, Skarsvik S, Lindström A, Zetterström O, Duchén K

机构信息

Division of Paediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Science, University of Linköping, Linköping, Sweden.

出版信息

Scand J Immunol. 2007 Nov;66(5):591-8. doi: 10.1111/j.1365-3083.2007.02010.x. Epub 2007 Sep 14.

DOI:10.1111/j.1365-3083.2007.02010.x
PMID:17868259
Abstract

Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1beta were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-alpha was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.

摘要

T淋巴细胞的最佳激活需要T细胞表面分子与其在树突状细胞(DC)上表达的配体相互作用提供的共刺激信号。我们研究了从健康个体和桦树过敏哮喘个体的单核细胞分化而来,并通过猫和桦树过敏原及脂多糖刺激进一步成熟的DC在表型受体表达上是否存在差异。在过敏个体和健康个体的单核细胞衍生DC中检测到DC表面标志物的相似表达,包括HLA-DR、CD80、CD86、CD83、CD1a和CD11c。与未刺激的细胞相比,来自健康供体的细胞无论受何种抗原刺激,CD80和双CD80/CD86共刺激分子的激活情况相似。对于过敏个体的细胞,与用猫和脂多糖刺激的细胞相比,桦树过敏原单独或与CD80/CD86联合使用时,均无法产生相同程度的CD80表达增加。两组受试者未刺激的DC上清液中IL-6、IL-8、IL-10、MCP-1/MCAF和MIP-1β的水平相似。相比之下,与过敏个体的DC上清液相比,健康受试者的DC上清液中IL-12p70和TNF-α的自发分泌更高。与过敏个体相比,用桦树和脂多糖刺激后,健康个体样本中IL-12p70的分泌增加。结果表明,桦树过敏个体的DC特异性成熟受损,与桦树特异性免疫反应有关。过敏个体经桦树刺激的DC分泌的IL-12p70较低,这表明这些个体中不仅DC的成熟,而且这些细胞的特异性Th1功能似乎都受到了影响。

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