Deng Caishu, Goluszko Elzbieta, Tüzün Erdem, Yang Huan, Christadoss Premkumar
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
J Immunol. 2002 Jul 15;169(2):1077-83. doi: 10.4049/jimmunol.169.2.1077.
To provide direct genetic evidence for a role of IL-6 in experimental autoimmune myasthenia gravis (EAMG), IL-6 gene KO (IL-6(-/-)) mice in the C57BL/6 background were immunized with Torpedo californica acetylcholine receptor (AChR) and evaluated for EAMG. Only 25% of AChR-immunized IL-6(-/-) mice developed clinical EAMG compared to 83% of C57BL/6 (wild-type) mice. A significant reduction in the secondary anti-AChR Ab of IgG, IgG(2b), and IgG(2c), but not the primary or secondary IgM response was observed in AChR-immunized IL-6(-/-) mice, suggesting a possible defect in T cell help and class switching to anti-AChR IgG(2) isotype. The AChR-specific lymphocyte proliferative response, IFN-gamma, and IL-10 production were suppressed in AChR-immunized IL-6(-/-) mice. EAMG resistance in IL-6(-/-) mice was associated with a significant reduction in germinal center formation and decreased serum complement C3 levels. The data provide the first direct genetic evidence for a key role of IL-6 in the autoimmune response to AChR and in EAMG pathogenesis.
为了提供白细胞介素-6（IL-6）在实验性自身免疫性重症肌无力（EAMG）中作用的直接遗传学证据，用加州电鳐乙酰胆碱受体（AChR）免疫C57BL/6背景的IL-6基因敲除（IL-6(-/-)）小鼠，并对其进行EAMG评估。与83%的C57BL/6（野生型）小鼠相比，仅25%的经AChR免疫的IL-6(-/-)小鼠出现临床EAMG。在经AChR免疫的IL-6(-/-)小鼠中，观察到IgG、IgG(2b)和IgG(2c)的继发性抗AChR抗体显著减少，但原发性或继发性IgM反应未受影响，这表明T细胞辅助以及向抗AChR IgG(2)同种型的类别转换可能存在缺陷。在经AChR免疫的IL-6(-/-)小鼠中，AChR特异性淋巴细胞增殖反应、干扰素-γ（IFN-γ）和白细胞介素-10（IL-10）的产生均受到抑制。IL-6(-/-)小鼠对EAMG的抗性与生发中心形成显著减少和血清补体C3水平降低有关。这些数据为IL-6在针对AChR的自身免疫反应和EAMG发病机制中的关键作用提供了首个直接遗传学证据。
