Svelander Lena, Erlandsson Harris Helena, Lorentzen Johnny C, Trollmo Christina, Klareskog Lars, Bucht Anders
Karolinska Institutet, Stockholm, Sweden.
Arthritis Rheum. 2004 Jan;50(1):297-304. doi: 10.1002/art.11488.
To investigate whether CpG oligodeoxynucleotides (ODNs) can induce or accelerate arthritis in rats.
The CpG-induced response was studied by recording joint inflammation, cell activation in draining lymph nodes, and levels of the acute-phase reactant alpha(1)-acid glycoprotein (AGP) in sera. The role of T cells was investigated by in vivo administration of monoclonal antibodies specific for the T cell receptor alpha/beta (TCRalpha/beta), followed by analysis of cell phenotypes by flow cytometry.
One intradermal injection of CpG ODN emulsified with Freund's incomplete adjuvant (IFA) induced arthritis in LEW and LEW.1AV1 rats, while the control ODN sequence without CpG motifs or IFA alone did not trigger disease. The CpG/IFA and control-ODN/IFA injections induced lymphoplasia as well as elevated levels of interleukin-1beta and interferon-gamma messenger RNA in lymph nodes. The arthritis was preceded by elevated levels of AGP in serum. In vivo administration of anti-TCRalpha/beta antibodies after disease induction caused decreased expression of the TCR-CD3 complex on circulating T cells and ameliorated the arthritis.
We demonstrated that injection with immunostimulatory CpG, both in phosphorothioate-modified and native forms, can induce a T cell-dependent joint-specific inflammation in LEW and LEW.1AV1 rat strains. This arthritis is preceded by signs of activation of the innate immune system. Since unmethylated CG dinucleotides are common in bacterial DNA but rare in mammalian DNA, our results indicate that exposure to bacterial DNA during infection may contribute to arthritis induction by amplifying the innate immune response.
研究CpG寡脱氧核苷酸（ODN）是否能诱导或加速大鼠关节炎。
通过记录关节炎症、引流淋巴结中的细胞活化以及血清中急性期反应物α(1)-酸性糖蛋白（AGP）的水平来研究CpG诱导的反应。通过体内给予针对T细胞受体α/β（TCRα/β）的单克隆抗体，随后通过流式细胞术分析细胞表型，来研究T细胞的作用。
一次皮内注射用弗氏不完全佐剂（IFA）乳化的CpG ODN可在LEW和LEW.1AV1大鼠中诱导关节炎，而无CpG基序的对照ODN序列或单独的IFA不会引发疾病。CpG/IFA和对照ODN/IFA注射可诱导淋巴组织增生以及淋巴结中白细胞介素-1β和干扰素-γ信使核糖核酸水平升高。关节炎发生前血清中AGP水平升高。疾病诱导后体内给予抗TCRα/β抗体导致循环T细胞上TCR-CD3复合物的表达降低，并改善了关节炎。
我们证明，注射硫代磷酸酯修饰的和天然形式的免疫刺激性CpG均可在LEW和LEW.1AV1大鼠品系中诱导T细胞依赖性关节特异性炎症。这种关节炎之前有先天免疫系统激活的迹象。由于未甲基化的CG二核苷酸在细菌DNA中常见但在哺乳动物DNA中罕见，我们的结果表明，感染期间暴露于细菌DNA可能通过放大先天免疫反应而促成关节炎的诱导。
