Anti-CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice
Anti-CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice
复制标题
抗 CD40 单克隆抗体可改善小鼠实验性自身免疫性葡萄膜视网膜炎
DOI：
10.1111/vop.12799
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发表时间：
2020
影响因子：
1.6
通讯作者：
Feilan Chen
中科院分区：
文献类型：
--
作者：
Lei Xu;Jie Gao;Yongquan Pan;Na Tian;Mingzhong He;Lei Jin;Feilan Chen
目的探讨CD40对B10.RIII小鼠实验性自身免疫性葡萄膜视网膜炎(EAU)眼部炎症的影响。实验动物采用完全弗氏佐剂中的光感受器间视黄醇结合蛋白(IRBP)161-180对EAU敏感的B10.RIII小鼠进行皮下免疫，并在第7、14、21天进行临床和病理评估。免疫后28和35。从免疫后第 7 天到第 14 天，每隔一天将抗 CD40 抗体腹腔注射到小鼠体内。注射磷酸盐缓冲盐水（PBS）的EAU小鼠作为对照。 程序免疫后第0、7、14和21天通过流式细胞术评估脾细胞中CD11c+CD40+树突状细胞（DC）、CD11c+MHC-II+DC和CD11c+CD40+MHC-II+DC的频率。通过 ELISA 评估 CD11c+DC 中肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-6 的产生。使用改良的 MTT 细胞增殖测定法评估 IRBP 特异性淋巴细胞增殖。结果 CD11c+CD40+DC、CD11c+MHC-II+DC 和 CD11c+CD40+MHC-II+DC 的数量在 EAU 发病时增加，在疾病严重程度达到顶峰，并持续保持在高水平直至第 21 天。抗 CD40 抗体治疗显着减轻了与 EAU 相关的临床和病理活动。 EAU。与对照小鼠相比，抗体处理的 EAU 小鼠在脾细胞中显示出很少的 CD11c+CD40+DC 和 CD11c+CD40+MHC-II+DC 频率。抗 CD40 抗体显着抑制 EAU 小鼠中 IRBP 特异性淋巴细胞增殖以及 DC 产生 TNF-α 和 IL-6。 结论 EAU 小鼠脾细胞中 CD40 和主要组织相容性复合物 (MHC) II 类分子表达增加与炎症活动相关。抗 CD40 治疗可以通过抑制全身 IRBP 特异性免疫反应来显着减弱 EAU 活性。
ObjectiveTo investigate the effects of CD40 on ocular inflammation in experimental autoimmune uveoretinitis (EAU) in B10.RIII mice.Animals studiedEAU‐susceptible B10.RIII mice were subcutaneously immunized with interphotoreceptor retinoid‐binding protein (IRBP) 161‐180 in complete Freund's adjuvant and evaluated clinically and pathologically on days 7, 14, 21, 28, and 35 postimmunization. Anti‐CD40 antibody was intraperitoneally injected into mice every other day from days 7 to 14 postimmunization. Phosphate‐buffered saline (PBS)‐injected EAU mice were used as the controls.ProceduresThe frequencies of CD11c+CD40+dendritic cells (DCs), CD11c+MHC‐II+DCs, and CD11c+CD40+MHC‐II+DCs in splenocytes were evaluated by flow cytometry on days 0, 7, 14, and 21 after immunization. Tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 production in CD11c+DCs was assessed by ELISA. IRBP‐specific lymphocyte proliferation was assessed using a modified MTT cell proliferation assay.ResultsThe number of CD11c+CD40+DCs, CD11c+MHC‐II+DCs, and CD11c+CD40+MHC‐II+DCs increased at the onset of EAU, peaked at the height of disease severity, and was sustained at a high level until day 21. Treatment with anti‐CD40 antibody significantly alleviated clinical and pathological activities related to EAU. Compared with the control mice, antibody‐treated EAU mice showed few CD11c+CD40+DC and CD11c+CD40+MHC‐II+DC frequencies in splenocytes. The anti‐CD40 antibody significantly suppressed IRBP‐specific lymphocyte proliferation and TNF‐α and IL‐6 production by DCs in EAU mice.ConclusionsThe increased expression of CD40 and major histocompatibility complex (MHC) class II molecules in the splenocytes of EAU mice were correlated with inflammatory activity. Anti‐CD40 treatment can significantly attenuate EAU activity by inhibiting systemic IRBP‐specific immune responses.