Matsui K, Nishikawa A
Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan.
Clin Exp Allergy. 2003 Jun;33(6):842-8. doi: 10.1046/j.1365-2222.2003.01666.x.
Our previous study demonstrated that lipoteichoic acid (LTA) from Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously with an allergen. However, the effects of LTA on allergen-specific IgE production in such sensitized mice have not been elucidated.
The purpose of this study was to determine the effects of LTA from S. aureus on allergen-specific IgE production in mice sensitized percutaneously with a house dust mite antigen (MA).
Mice were sensitized with a single topical application of MA and/or LTA to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE antibodies in sera from sensitized mice were detected by an enzyme-linked immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph nodes of sensitized mice were analysed by flow-cytometry (FACS).
Simultaneous sensitization with MA and LTA increased IgE production 3 weeks later, significantly more than sensitization with MA alone. FACS analysis of CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen-presenting cells such as B lymphocytes and dendritic cells more than sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes showed that simultaneous sensitization with MA and LTA increased the number of CD40L-expressing Th cells more than sensitization with MA alone.
These results suggest that LTA enhances allergen-specific IgE production by a mechanism associated with up-regulation of CD40L-expressing Th cells and this might explain the role of skin colonization with S. aureus in AD patients.
我们之前的研究表明，金黄色葡萄球菌的脂磷壁酸（LTA）可诱导2型辅助性T细胞（Th2）倾向的皮炎，其在经过敏原经皮致敏的小鼠中类似于特应性皮炎（AD）患者所见的皮炎。然而，LTA对这种致敏小鼠中过敏原特异性IgE产生的影响尚未阐明。
本研究的目的是确定金黄色葡萄球菌的LTA对经屋尘螨抗原（MA）经皮致敏的小鼠中过敏原特异性IgE产生的影响。
将MA和/或LTA单次局部应用于屏障破坏的腹部皮肤使小鼠致敏。1至5周后，通过酶联免疫吸附测定（ELISA）检测致敏小鼠血清中的MA特异性IgE抗体。通过流式细胞术（FACS）分析致敏小鼠淋巴结中CD40阳性（CD40 +）和CD4阳性（CD4 +）细胞的B7.1（CD80）、B7.2（CD86）和CD40L分子的表达。
MA和LTA同时致敏3周后IgE产生增加，显著高于单独用MA致敏。对致敏小鼠淋巴结中CD40 +细胞的FACS分析表明，与单独用MA致敏相比，MA和LTA同时致敏不会增强诸如B淋巴细胞和树突状细胞等抗原呈递细胞的CD80或CD86表达。然而，对淋巴结中CD4 +细胞的分析表明，与单独用MA致敏相比，MA和LTA同时致敏增加了表达CD40L的Th细胞数量。
这些结果表明，LTA通过与表达CD40L的Th细胞上调相关的机制增强过敏原特异性IgE产生，这可能解释了金黄色葡萄球菌皮肤定植在AD患者中的作用。
