CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness
CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness
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DOI：
10.1164/ajrccm.161.3.9905046
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发表时间：
2000-03-01
影响因子：
24.7
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Haczku, A;Takeda, K;Gelfand, EW
在过敏性致敏的小鼠模型中，比较了抗CD23单抗(B3B4)在CD23缺陷和CD23过表达小鼠中的作用。(1)与未致敏的小鼠相比，抗CD23抗体的治疗方案为：10d的OA气雾剂暴露和腹腔致敏后气雾剂激发。在两种方案中，抗CD23抗体均显著降低BALB/c和野生型CD23(+/+)小鼠的IgE和Ig G(1)水平，消除嗜酸性粒细胞增多，使AHR正常化，而CD23(-/-)小鼠则无此变化。这些变化与干扰素-γ的升高和IL-4的产生减少有关，提示CD23结合不仅影响IgE的产生，而且可能影响变态反应性AHR的Th1/Th2失衡。与CD23(+/+)野生型相比，CD23缺失的基因缺陷小鼠在致敏和呼吸道攻击后显著增加了OA特异性IgE和Ig G(1)水平、呼吸道嗜酸性粒细胞增多和AHR。致敏和激发的CD23转基因小鼠也出现嗜酸性气道炎和乙酰甲胆碱高反应性，但这些动物的AHR、BAL和组织嗜酸性粒细胞增多的程度与脾T和B细胞上CD23的表达水平呈显著负相关，表明CD23在变态反应性AHR的发生发展中具有限制作用。
The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG(1) with airway eosinophilia and AHR when compared with nonsensitized animals, Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG(1) levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23(+/+) mice but not in CD23(-/-) mice, These changes were associated with increases in IFN-gamma and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA-specific IgE and IgG(1) levels, airway eosinophilia, and AHR when compared with CD23(+/+) wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness, However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR.