Induction of mucosal tolerance with recombinant Hev b 1 and recombinant Hev b 3 for prevention of latex allergy in BALB/c mice
Induction of mucosal tolerance with recombinant Hev b 1 and recombinant Hev b 3 for prevention of latex allergy in BALB/c mice
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DOI：
10.1046/j.1365-2249.2003.02210.x
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发表时间：
2003-08-01
影响因子：
4.6
通讯作者：
Weidermann, U
中科院分区：
文献类型：
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作者：
Hufnagl, K;Wagner, B;Weidermann, U
在经常接触乳胶产品的个体中，例如医护人员 (HCW) 和脊柱裂 (SB) 患者，对巴西橡胶树乳胶 I 型过敏的患病率特别高。乳胶过敏的治疗似乎存在问题，因为预防措施（例如避免过敏原）并不总是可行，而且使用标准化乳胶提取物的常规免疫疗法也没有常规进行。因此，本研究的目的是使用 HCW 和 SB 患者的两种主要乳胶过敏原 Hev b 1 和 Hev b 3 来建立乳胶过敏小鼠模型，以进行致敏。在该模型中测试了基于重组过敏原诱导粘膜耐受性的预防措施。用重组(r)Hev b 1或rHev b 3腹腔内免疫的雌性BALB/c小鼠在体内和体外表现出强烈的免疫反应。致敏前用 rHev b 1 和 rHev b 3 鼻内治疗可降低过敏原特异性 IgG1/IgE 水平，并显着抑制过敏原诱导的嗜碱性粒细胞脱粒。此外，用两种过敏原预处理后，体外淋巴细胞增殖和细胞因子产生（IL-4、IL-5、IFN-γ）显着受到抑制。鼻内预处理后，抑制性细胞因子，如白细胞介素（IL）-10和转化生长因子（TGF）-β保持不变，表明无反应机制，而不是主动免疫抑制机制。综上所述，这些结果表明，用重组过敏原诱导粘膜耐受可以提供一种有前途的乳胶过敏预防策略。
The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure to latex products, such as health-care workers (HCW) and patients with spina bifida (SB). Treatment of latex allergy seems problematic as preventive measures, such as allergen avoidance, are not always possible and conventional immunotherapy with standardized latex extracts is not performed routinely. Thus, the aim of the present study was to establish a mouse model of latex allergy using two major latex allergens for HCWs and SB patients, Hev b 1 and Hev b 3, for sensitization. Prophylactic measures on the basis of mucosal tolerance induction with the recombinant allergens were tested in this model. Female BALB/c mice immunized intraperitoneally with recombinant (r)Hev b 1 or rHev b 3 displayed strong immune responses in vivo and in vitro. Intranasal treatment with rHev b 1 and rHev b 3 prior to sensitization led to reduced allergen-specific IgG1/IgE levels and significantly suppressed allergen-induced basophil degranulation. Moreover, lymphocyte proliferation and cytokine production (IL-4, IL-5, IFN-gamma) in vitro were significantly suppressed after pretreatment with both allergens. Suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-beta, remained unchanged after the intranasal pretreatment, indicating mechanism of anergy rather than active immunosuppression. Taken together, these results suggest that mucosal tolerance induction with recombinant allergens could present a promising prevention strategy against latex allergy.