Bellinghausen Iris, Sudowe Stephan, König Bettina, Reske-Kunz Angelika B, Knop Jürgen, Saloga Joachim
Department of Dermatology, University of Mainz, Mainz, Germany.
Int Arch Allergy Immunol. 2006;141(1):61-9. doi: 10.1159/000094255. Epub 2006 Jun 28.
It is well known that the immunoregulatory cytokine interleukin (IL)-10 inhibits the accessory function of human dendritic cells (DC) in vitro. Recently, we have shown that these IL-10 DC inhibit the production of T helper cell 1 (Th1) and T helper cell 2 (Th2) cytokines by T cells from atopic individuals in vitro. The current study was set out to analyze whether IL-10 DC also exert inhibitory effects in vivo in a murine model of allergy to ovalbumin adsorbed to the adjuvant aluminium hydroxide (OVA/alum).
OVA-pulsed or unpulsed bone marrow-derived DC, treated with IL-10 or left untreated during generation, were injected intravenously into BALB/c mice prior to and during OVA/alum sensitization, and sera and immune responses of mesenterial lymph node cells were analyzed. Additionally, bronchoalveolar lavage was performed after intranasal challenge with OVA.
Treatment of BALB/c mice with OVA-pulsed DC led to a significantly enhanced proliferation as well as Th2 (IL-4, IL-5), Th1 (interferon-gamma) and IL-10 cytokine production after restimulation of lymph node cells with OVA in vitro compared with OVA immunization alone. In contrast, using OVA-pulsed IL-10 DC for transfer, proliferation and cytokine production by lymph node cells were not enhanced. OVA-specific immunoglobulin G1 (IgG1) and IgG2a production were significantly increased after transfer of OVA-pulsed DC and OVA-pulsed IL-10 DC, respectively, whereas anti-OVA IgE production and airway eosinophilia remained unchanged.
Our data indicate that IL-10 treatment of DC decreases the Th1 and Th2 stimulatory capacity of DC but does not actually inhibit systemic (IgE) and local (airway inflammation) allergen-specific immune responses in a murine model of allergy.
众所周知,免疫调节细胞因子白细胞介素(IL)-10在体外可抑制人树突状细胞(DC)的辅助功能。最近,我们发现这些IL-10 DC在体外可抑制特应性个体T细胞产生辅助性T细胞1(Th1)和辅助性T细胞2(Th2)细胞因子。本研究旨在分析在对吸附于佐剂氢氧化铝(OVA/明矾)的卵清蛋白过敏的小鼠模型中,IL-10 DC在体内是否也发挥抑制作用。
在OVA/明矾致敏之前及期间,将在生成过程中用IL-10处理或未处理的OVA脉冲或未脉冲的骨髓来源DC静脉注射到BALB/c小鼠体内,然后分析血清及肠系膜淋巴结细胞的免疫反应。此外,在用OVA进行鼻内激发后进行支气管肺泡灌洗。
与单独进行OVA免疫相比,用OVA脉冲DC处理BALB/c小鼠后,体外再用OVA刺激淋巴结细胞,其增殖以及Th2(IL-4、IL-5)、Th1(干扰素-γ)和IL-10细胞因子的产生均显著增强。相比之下,使用OVA脉冲的IL-10 DC进行转移时,淋巴结细胞的增殖和细胞因子产生并未增强。分别转移OVA脉冲DC和OVA脉冲的IL-10 DC后,OVA特异性免疫球蛋白G1(IgG1)和IgG2a的产生显著增加,而抗OVA IgE的产生和气道嗜酸性粒细胞增多保持不变。
我们的数据表明,用IL-10处理DC可降低DC的Th1和Th2刺激能力,但在小鼠过敏模型中实际上并未抑制全身性(IgE)和局部性(气道炎症)过敏原特异性免疫反应。