首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis.
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Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis.

机译:眼表APC对于自身反应性T细胞介导的实验性自身免疫性泪道角膜结膜炎是必需的。

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摘要

As specialized sentinels between the innate and adaptive immune response, APCs are essential for activation of Ag-specific lymphocytes, pathogen clearance, and generation of immunological memory. The process is tightly regulated; however, excessive or atypical stimuli may ignite activation of APCs in a way that allows self-Ag presentation to autoreactive T cells in the context of the necessary costimulatory signals, ultimately resulting in autoimmunity. Studies in both animal models and patients suggest that dry eye is a chronic CD4(+) T cell-mediated ocular surface autoimmune-based inflammatory disease. Using a desiccating stress-induced mouse model of dry eye, we establish the fundamental role of APCs for both the generation and maintenance of ocular-specific autoreactive CD4(+) T cells. Subconjunctival administration of liposome-encapsulated clodronate efficiently diminished resident ocular surface APCs, inhibited the generation of autoreactive CD4(+) T cells, and blocked their ability to cause disease. APC-dependent CD4(+) T cell activation required intact draining cervical lymph nodes, as cervical lymphadenectomy also inhibited CD4(+) T cell-mediated dry eye disease. In addition, local depletion of peripheral conjunctival APCs blocked the ability of dry eye-specific CD4(+) T cells to accumulate within the ocular surface tissues, suggesting that fully primed and targeted dry eye-specific CD4(+) T cells require secondary activation by resident ocular surface APCs for maintenance and effector function. These data demonstrate that APCs are necessary for the initiation and development of experimental dry eye and support the standing hypothesis that dry eye is a self-Ag-driven autoimmune disease.
机译:作为先天性和适应性免疫反应之间的专门哨兵,APC对激活Ag特异性淋巴细胞,病原体清除和产生免疫记忆至关重要。该过程受到严格监管;然而,过多或非典型的刺激可能以某种方式点燃APC的激活,从而在必要的共刺激信号的情况下将自身Ag呈递给自身反应性T细胞,最终导致自身免疫。在动物模型和患者中的研究均表明,干眼症是一种慢性CD4(+)T细胞介导的眼表自身免疫性炎症性疾病。使用干燥的应力引起的干眼小鼠模型,我们建立了APC在产生和维持眼特异性自身反应性CD4(+)T细胞方面的基本作用。结膜下给药脂质体包裹的氯膦酸盐可有效减少驻留的眼表APC,抑制自身反应性CD4(+)T细胞的生成,并阻止其引起疾病的能力。 APC依赖的CD4(+)T细胞活化需要完整的引流颈淋巴结,因为颈淋巴结清扫术也抑制CD4(+)T细胞介导的干眼病。此外,周围结膜APC的局部耗竭阻止了干眼特异性CD4(+)T细胞在眼表组织内积累的能力,表明完全引发和靶向的干眼特异性CD4(+)T细胞需要二次激活通过常驻眼表APC进行维护和效应器功能。这些数据表明,APC对于实验性干眼症的发生和发展是必需的,并支持干眼症是一种自身抗原驱动的自身免疫性疾病的假说。

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