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在特应性皮炎的小鼠模型中,局部暴露超抗原可诱导CD8 + T细胞在表皮积聚、引发混合性Th1/Th2型皮炎并大量产生IgE抗体。

Topical superantigen exposure induces epidermal accumulation of CD8+ T cells, a mixed Th1/Th2-type dermatitis and vigorous production of IgE antibodies in the murine model of atopic dermatitis.

作者信息

Savinko Terhi, Lauerma Antti, Lehtimäki Sari, Gombert Michael, Majuri Marja-Leena, Fyhrquist-Vanni Nanna, Dieu-Nosjean Marie-Caroline, Kemeny Lajos, Wolff Henrik, Homey Bernhard, Alenius Harri

机构信息

Laboratory of Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.

出版信息

J Immunol. 2005 Dec 15;175(12):8320-6. doi: 10.4049/jimmunol.175.12.8320.

DOI:10.4049/jimmunol.175.12.8320
PMID:16339573
Abstract

Patients with atopic dermatitis (AD) have repeated cutaneous exposure to both environmental allergens and superantigen-producing strains of Staphylococcus aureus. We used a murine model of AD to investigate the role of staphylococcal enterotoxin B (SEB) in the modulation of allergen-induced skin inflammation. Mice were topically exposed to SEB, OVA, a combination of OVA and SEB (OVA/SEB), or PBS. Topical SEB and OVA/SEB exposure induced epidermal accumulation of CD8+ T cells and TCRVbeta8+ cells in contrast to OVA application, which induced a mainly dermal infiltration of CD4+ cells. SEB and OVA/SEB exposure elicited a mixed Th1/Th2-associated cytokine and chemokine expression profile within the skin. Restimulation of lymph node cells from OVA- and OVA/SEB-exposed mice with OVA elicited strong production of IL-13 protein, whereas substantial amounts of IFN-gamma protein were detected after SEB stimulation of cells derived from SEB- or OVA/SEB-exposed mice. Topical SEB treatment elicited vigorous production of SEB-specific IgE and IgG2a Abs and significantly increased the production of OVA-specific IgE and IgG2a Abs. The present study shows that topical exposure to SEB provokes epidermal accumulation of CD8+ T cells, a mixed Th2/Th1 type dermatitis and vigorous production of specific IgE and IgG2a Abs, which can be related to the chronic phase of atopic skin inflammation.

摘要

特应性皮炎(AD)患者的皮肤反复暴露于环境过敏原和产超抗原的金黄色葡萄球菌菌株。我们使用AD小鼠模型来研究葡萄球菌肠毒素B(SEB)在调节变应原诱导的皮肤炎症中的作用。将小鼠局部暴露于SEB、卵清蛋白(OVA)、OVA与SEB的组合(OVA/SEB)或磷酸盐缓冲液(PBS)。与仅应用OVA主要诱导真皮层CD4+细胞浸润不同,局部暴露于SEB和OVA/SEB可诱导CD8+T细胞和TCRVbeta8+细胞在表皮积聚。SEB和OVA/SEB暴露可引发皮肤内与Th1/Th2相关的细胞因子和趋化因子的混合表达谱。用OVA再次刺激OVA和OVA/SEB暴露小鼠的淋巴结细胞可诱导IL-13蛋白的大量产生,而用SEB刺激SEB或OVA/SEB暴露小鼠来源的细胞后可检测到大量的IFN-γ蛋白。局部SEB治疗可引发大量SEB特异性IgE和IgG2a抗体的产生,并显著增加OVA特异性IgE和IgG2a抗体的产生。本研究表明,局部暴露于SEB可引发CD8+T细胞在表皮积聚、Th2/Th1混合型皮炎以及大量特异性IgE和IgG2a抗体的产生,这可能与特应性皮肤炎症的慢性期有关。

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