Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice
Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice
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DOI：
10.4049/jimmunol.172.7.4503
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Kamradt, T
中科院分区：
文献类型：
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作者：
Schubert, D;Maier, B;Kamradt, T
风湿性关节炎是一种慢性炎症性疾病，主要影响关节。在类风湿性关节炎中触发自身免疫反应的致关节炎自身抗原的研究主要集中在软骨或关节特异性抗原上。在这项研究中，我们表明，用普遍表达的糖酵解酶葡萄糖-6-磷酸异构酶（G6 PI）免疫会诱导正常小鼠出现严重的外周对称性多关节炎。在基因未改变的小鼠中，T细胞对于G6 PI诱导的关节炎的诱导和效应阶段都是不可或缺的。关节炎通过CD 4（+）细胞的消耗而治愈。相比之下，Abs和Fc γ R（+）效应细胞是必需的，但不足以在基因未改变的小鼠G6 PI诱导的关节炎。因此，正常小鼠中G6 PI诱导的关节炎的复杂发病机制与转基因K/B × N模型中自发发生的关节炎有很大不同，在转基因K/B × N模型中，单独抗G6 PI的Ab足以诱导疾病。G6 PI诱导的关节炎首次证明了在遗传未改变的小鼠中通过全身性自身免疫诱导器官特异性疾病。系统性自身免疫反应诱导的关节炎的诱导期和效应期都可以在该模型中进行分析，并评估预防和治疗策略。
Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the joints. The search for arthritogenic autoantigens that trigger autoimmune responses in rheumatoid arthritis has largely focused on cartilage- or joint-specific Ags. In this study, we show that immunization with the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) induces severe peripheral symmetric polyarthritis in normal mice. In genetically unaltered mice, T cells are indispensable for both the induction and the effector phase of G6PI-induced arthritis. Arthritis is cured by depletion of CD4(+) cells. In contrast, Abs and FcgammaR(+) effector cells are necessary but not sufficient for G6PI-induced arthritis in genetically unaltered mice. Thus, the complex pathogenesis of G6PI-induced arthritis in normal mice differs strongly from the spontaneously occurring arthritis in the transgenic K/B x N model where Abs against G6PI alone suffice to induce the disease. G6PI-induced arthritis demonstrates for the first time the induction of organ-specific disease by systemic autoimmunity in genetically unaltered mice. Both the induction and effector phase of arthritis induced by a systemic autoimmune response can be dissected and preventive and therapeutic strategies evaluated in this model.