Vanderheyde N, Verhasselt V, Goldman M, Willems F
Laboratory of Experimental Immunology and Centre de Recherche Interuniversitaire en Vaccinologie, Université Libre de Bruxelles, Brussels, Belgium.
Transplantation. 1999 May 27;67(10):1342-7. doi: 10.1097/00007890-199905270-00009.
The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC. Here, we analyzed how methylprednisolone (MP) might affect the function and maturation of human DC.
Human DC were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin (IL)4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L). DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity.
Although MP did not affect viability of DC, it enhanced their antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. In contrast, when DC were stimulated by 3T6-CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC were deficient in their ability to elicit proliferative responses of CD4+CD45RA+ allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13. CONCLUSION. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.
本研究旨在更明确地界定糖皮质激素如何影响原代人T细胞反应。树突状细胞（DC*）是能够激活初始T细胞的最有效的抗原呈递细胞。先前的研究表明，地塞米松会损害小鼠DC的功能。在此，我们分析了甲泼尼龙（MP）可能如何影响人DC的功能和成熟。
从在粒细胞巨噬细胞集落刺激因子和白细胞介素（IL）-4中培养的外周血单核细胞生成人DC。通过脂多糖（LPS）或用CD40配体基因转染的成纤维细胞（3T6-CD40L）诱导DC成熟。通过流式细胞术分析DC表型，通过ELISA检测其细胞因子产生。在混合淋巴细胞反应中评估DC激活初始T细胞的能力。
尽管MP不影响DC的活力，但它增强了DC的抗原摄取并下调了CD86的基础表达。DC的CD80和CD54表达略有下降，而HLA-DR表达未改变。通过抑制CD86、CD80和CD54上调、CD83诱导以及TNF-α、IL-6和IL-12的产生评估，MP可阻止LPS诱导的DC成熟。相反，当DC由3T6-CD40L刺激时，MP仅阻止IL-12的合成。此外，经MP处理的DC引发CD4+CD45RA+同种异体T细胞增殖反应的能力以及其干扰素（IFN）-γ、IL-5和IL-13的合成均存在缺陷。结论：糖皮质激素对人DC具有强大的抑制作用，从而抑制原代T细胞反应的诱导。
