Piemonti L, Monti P, Allavena P, Leone B E, Caputo A, Di Carlo V
Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, 20132 Milan, Italy.
Int Immunol. 1999 Sep;11(9):1519-26. doi: 10.1093/intimm/11.9.1519.
We have investigated the effect of glucocorticoids (GC) on antigen uptake molecule expression and on endocytic activity of human dendritic cells (DC). Human monocyte-derived DC were differentiated in vitro for 7 days with granulocyte macrophage colony stimulating factor and IL-4 in the presence or absence of dexamethasone 10(-8) M (Dex). Dex-treated DC showed an enhancement of mannose receptor (MR)-mediated endocytosis (measured as uptake of FITC-dextran) and of fluid-phase endocytosis [measured as uptake of Lucifer yellow (LY)] The effect was dose dependent and correlated with the length of exposure to Dex. The expression of receptors involved in antigen capture was investigated by FACS analysis. Dex up-regulates MR, CD16 and CD32 expression on DC. After maturation with tumor necrosis factor-alpha or CD40 ligand in Dex-treated DC, despite a reduction induced by maturation the endocytic activity of FITC-dextran and LY, the expression of MR, CD16 and CD32 remained higher than in control DC. In view of the fact that antigen capture was increased in cells cultured with Dex, we evaluated the ability to present soluble antigen that needs to be taken up and processed. Cells differentiated in the presence of Dex showed much lower efficiency in presenting tetanus toxin to specific autologous T cell lines. In conclusion our data suggest a new mechanism by which GC may influence immune responses. In fact with the increase in endocytic activity, Dex favors the scavenging of antigen from the external milieu, decreasing antigen concentration and availability, and simultaneously inhibiting the capacity to stimulate T cells.
我们研究了糖皮质激素（GC）对人树突状细胞（DC）抗原摄取分子表达及内吞活性的影响。人单核细胞来源的DC在体外分别于存在或不存在10⁻⁸ M地塞米松（Dex）的情况下，用粒细胞巨噬细胞集落刺激因子和IL-4分化7天。经Dex处理的DC显示甘露糖受体（MR）介导的内吞作用（以FITC-葡聚糖摄取量衡量）和液相内吞作用[以异硫氰酸荧光素（LY）摄取量衡量]增强。该作用呈剂量依赖性，且与Dex暴露时间相关。通过流式细胞术分析研究了参与抗原捕获的受体表达。Dex上调DC上MR、CD16和CD32的表达。在用肿瘤坏死因子-α或CD40配体使经Dex处理的DC成熟后，尽管成熟导致FITC-葡聚糖和LY的内吞活性降低，但MR、CD16和CD32的表达仍高于对照DC。鉴于在用Dex培养的细胞中抗原捕获增加，我们评估了呈递需要摄取和加工的可溶性抗原的能力。在存在Dex的情况下分化的细胞向特定自体T细胞系呈递破伤风毒素的效率要低得多。总之，我们的数据提示了一种GC可能影响免疫反应的新机制。实际上，随着内吞活性的增加，Dex有利于从外部环境中清除抗原，降低抗原浓度和可利用性，同时抑制刺激T细胞的能力。
