Gulhane Military School of Medicine, Ankara, Turkey.
Clin Exp Rheumatol. 2009 Mar-Apr;27(2 Suppl 53):S37-42.
Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). Interferon (IFN)-alpha which has an ability to promote strong Th1 type immune response has been shown to increase in patients with BD. In order to clarify if plasmacytoid dendritic cells (pDCs) abnormally respond to a stimulus in patients with BD, we investigated the levels of intracellular IFN-alpha and beta in pDCs with or without CpG D ODN stimulation.
The study population consisted of 8 patients with clinically active BD, 8 ankylosing spondilitis (AS) patients having active disease and 11 healthy volunteers. pDC subsets in peripheral blood mononuclear cells (PBMCs) cultures were analysed by flow cytometry.
The percentage of IFN-alpha+ pDCs in unstimulated PBMCs cultures from patients BD was significantly higher (p=0.036) than in AS and HC. But this difference disappeared in stimulated PBMCs cultures (p=0.167). The mean fluorescence intensity (MFI) of IFN-alpha+ pDCs in stimulated PBMCs cultures of BD patients was significantly higher than those from patients with AS and HC. The percentage of IFN-beta+ pDCs in unstimulated PBMCs cultures from patients with BD and AS was significantly higher (p=0.004) than in HC. But this difference was not significant in stimulated PBMCs cultures (p=0.694). When compared to healthy subjects, the MFI of IFN-beta + pDCs in unstimulated and stimulated PBMCs cultures from patients with BD and AS was not different (p=0.287, p=0.152, respectively). In patients with BD, the percentage and MFI of IFN-alpha+ pDCs were higher (p=0.012 for all) in stimulated PBMCs cultures as compared to unstimulated ones.
We suggest that increased frequency of IFN-alpha+ pDC in BD patients and the higher sensitiveness of these cells to CpG D ODN stimulus contribute to high serum IFN-alpha levels found in these patients which eventually resulted in Th1 type immune response.
有几条证据表明,贝切特病(BD)存在极化的辅助性 T 细胞 1(Th1)免疫应答。具有促进强烈 Th1 型免疫应答能力的干扰素(IFN)-α已被证明在 BD 患者中增加。为了阐明 BD 患者的浆细胞样树突状细胞(pDC)是否异常对刺激物作出反应,我们研究了 pDC 在有无 CpG 寡脱氧核苷酸(ODN)刺激时细胞内 IFN-α和 IFN-β的水平。
研究人群包括 8 例有临床活动的 BD 患者、8 例活动期强直性脊柱炎(AS)患者和 11 名健康志愿者。通过流式细胞术分析外周血单个核细胞(PBMC)培养物中的 pDC 亚群。
BD 患者未刺激 PBMC 培养物中 IFN-α+pDC 的百分比明显高于 AS 和 HC(p=0.036)。但在刺激 PBMC 培养物中,这种差异消失(p=0.167)。BD 患者刺激 PBMC 培养物中 IFN-α+pDC 的平均荧光强度(MFI)明显高于 AS 和 HC 患者。BD 和 AS 患者未刺激 PBMC 培养物中 IFN-β+pDC 的百分比明显高于 HC(p=0.004)。但在刺激 PBMC 培养物中,这种差异无统计学意义(p=0.694)。与健康受试者相比,BD 和 AS 患者未刺激和刺激 PBMC 培养物中 IFN-β+pDC 的 MFI 无差异(p=0.287,p=0.152)。BD 患者刺激 PBMC 培养物中 IFN-α+pDC 的百分比和 MFI 均高于未刺激 PBMC 培养物(p=0.012 均)。
我们认为,BD 患者中 IFN-α+pDC 的频率增加,以及这些细胞对 CpG ODN 刺激的敏感性增加,导致这些患者血清 IFN-α 水平升高,最终导致 Th1 型免疫应答。