Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B cell priming and not impairment in antigen presentation.
Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B cell priming and not impairment in antigen presentation.
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在抗原引发前预刺激 Toll 样受体 4 抑制体内抗体产生是由 B 细胞引发缺陷引起的，而不是抗原呈递受损所致。
DOI：
10.1093/intimm/dxs096
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发表时间：
2013
影响因子：
4.4
通讯作者：
and Masao Kimoto
中科院分区：
文献类型：
--
作者：
Nurlaely Mida Rachmawati;Kenji Fukudome;Naoko Tsuneyoshi;Uleng Bahrun;Hiroki Tsukamoto;Tsutomu Yanagibashi;Yoshinori Nagai;Kiyoshi Takatsu;Shoichiro Ohta;and Masao Kimoto
Toll 样受体 4 (TLR4) 的刺激不仅会诱导先天性免疫反应，还会诱导适应性免疫反应，并被认为可以发挥佐剂作用。除了这些积极作用之外，TLR4 的预刺激还可诱导内毒素耐受，使动物对随后的脂多糖 (LPS) 致命挑战无反应。我们检查了使用激动性抗 TLR4 mAb (UT12) 预刺激 TLR4 对体内抗体产生的影响。在初次和二次免疫之前预注射 UT12 完全抑制了抗原特异性抗体反应。细胞分析表明，这种抑制并非由于 T 细胞活化受损所致。因此，预注射 UT12 的小鼠中 T 辅助细胞活性并未受损。相比之下，预注射 UT12 的小鼠的 B 细胞启动有缺陷。预注射 UT12 可阻断 B 细胞上激活标记物（例如 CD69 和 CD86）的表达，这一观察结果支持了这一点。有趣的是，UT12预注射仅在初次免疫中显示出抑制作用，而在二次免疫中则没有显示出抑制作用。这些结果提供了有关抗体产生调节机制的重要信息，特别是在内毒素耐受状态下。
Stimulation of Toll-like receptor 4 (TLR4) induces not only innate but also adaptive immune responses, and has been suggested to exert adjuvant effects. Additional to such positive effects, pre-stimulation of TLR4 induces endotoxin tolerance where animals are unresponsive to subsequent lethal challenges with lipopolysaccharide (LPS). We examined the effects of pre-stimulation of TLR4 using an agonistic anti-TLR4 mAb (UT12) on antibody productionin vivo. Pre-injection of UT12 prior to both primary and secondary immunization completely inhibited antigen-specific antibody responses. Cellular analysis revealed that the inhibition was not due to impairment of T-cell activation. Accordingly, T-helper activities in UT12 pre-injected mice were not impaired. In contrast, B-cell priming was defective in UT12 pre-injected mice. The observation that the expression of activation markers such as CD69 and CD86 on B cells was blocked by UT12 pre-injection supports this. Interestingly, UT12 pre-injection only showed inhibitory effects at the primary and not the secondary immunization. These results provide important information concerning the regulatory mechanisms of antibody production, especially in endotoxin-tolerant states.