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一种用于过敏性免疫反应的人 - 重症联合免疫缺陷(SCID)小鼠模型:细菌超抗原增强皮肤炎症并抑制IgE产生。

A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production.

作者信息

Herz U, Schnoy N, Borelli S, Weigl L, Käsbohrer U, Daser A, Wahn U, Köttgen E, Renz H

机构信息

Department of Clinical Chemistry, Virchow-Klinikum of the Humboldt-Universität, Berlin, Germany.

出版信息

J Invest Dermatol. 1998 Mar;110(3):224-31. doi: 10.1046/j.1523-1747.1998.00119.x.

DOI:10.1046/j.1523-1747.1998.00119.x
PMID:9506440
Abstract

Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.

摘要

金黄色葡萄球菌慢性皮肤定植是特应性皮炎的一个众所周知的特征。本研究的目的是建立一种人 - SCID小鼠模型,以分析细菌超抗原在体内条件下对人类过敏性免疫反应可能发挥的作用。用对屋尘螨过敏原(Der p)致敏的特应性皮炎患者的外周血单个核细胞(每只小鼠2至9×10⁷个细胞)重建SCID小鼠。总抗体和Der p特异性抗体的产生需要以下条件:(i)注射Der p;(ii)存在CD14⁺抗原呈递细胞;(iii)白细胞介素 - 4,人可溶性白细胞介素 - 4受体对免疫球蛋白E产生的抑制作用表明了这一点。该模型用于研究超抗原葡萄球菌肠毒素B与Der p相比的免疫调节作用。在经腹腔重建的人 - SCID小鼠中,局部治疗在诱导皮肤炎症方面无效。因此,除了腹腔内转移外,还将特应性供体的外周血单个核细胞皮内注射。然后将这种重建的SCID小鼠通过皮肤暴露于Der p、葡萄球菌肠毒素B或两者的组合。葡萄球菌肠毒素B和Der p对表皮炎症和真皮T细胞浸润产生最大影响。单独的葡萄球菌肠毒素B效果较差,而Der p仅刺激真皮T细胞浸润。这些发现支持了细菌超抗原可作为过敏性皮肤炎症触发因素的假说。

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A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production.一种用于过敏性免疫反应的人 - 重症联合免疫缺陷(SCID)小鼠模型:细菌超抗原增强皮肤炎症并抑制IgE产生。
J Invest Dermatol. 1998 Mar;110(3):224-31. doi: 10.1046/j.1523-1747.1998.00119.x.
2
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.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。
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Epicutaneous sensitization with superantigen induces allergic skin inflammation.用超抗原进行表皮致敏可诱发过敏性皮肤炎症。
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Staphylococcal toxins augment specific IgE responses by atopic patients exposed to allergen.葡萄球菌毒素会增强特应性患者接触过敏原时的特异性IgE反应。
J Invest Dermatol. 1999 Feb;112(2):171-6. doi: 10.1046/j.1523-1747.1999.00492.x.
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Staphylococcal enterotoxin B affects in vitro IgE synthesis, interferon-gamma, interleukin-4 and interleukin-5 production in atopic eczema.葡萄球菌肠毒素B影响特应性皮炎患者体外IgE合成、γ干扰素、白细胞介素-4和白细胞介素-5的产生。
Int Arch Allergy Immunol. 1995 May-Jun;107(1-3):179-82. doi: 10.1159/000236970.
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Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis.将葡萄球菌肠毒素B涂抹于完整的正常皮肤和完整的特应性皮肤上会诱发皮炎。
Arch Dermatol. 1996 Jan;132(1):27-33.
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Impaired responses of peripheral blood mononuclear cells to staphylococcal superantigen in patients with severe atopic dermatitis: a role of T cell apoptosis.重度特应性皮炎患者外周血单个核细胞对葡萄球菌超抗原反应受损:T细胞凋亡的作用
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Responsiveness of peripheral blood mononuclear cells from normal and atopic donors to microbial superantigens.正常和特应性供体的外周血单个核细胞对微生物超抗原的反应性。
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Induction of IgE and IgG1 in human B cell cultures with staphylococcal superantigens: role of helper T cell interaction, resistance to interferon-gamma.用葡萄球菌超抗原在人B细胞培养物中诱导IgE和IgG1:辅助性T细胞相互作用的作用、对γ干扰素的抗性
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Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis.皮肤归巢(皮肤淋巴细胞相关抗原阳性)CD8 + T细胞对超抗原产生反应,并在特应性皮炎中导致嗜酸性粒细胞增多和IgE产生。
J Immunol. 1999 Jul 1;163(1):466-75.

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