Ardern-Jones Michael R, Black Antony P, Bateman Elizabeth A, Ogg Graham S
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5557-62. doi: 10.1073/pnas.0700733104. Epub 2007 Mar 19.
Although clinical and laboratory evidence support roles for both staphylococcal infection and environmental allergens in the pathogenesis of atopic dermatitis, human studies have largely considered these variables independently. We sought to test the hypothesis that staphylococcal superantigen influences the allergen-specific T cell response. We first mapped a Der p 1 epitope and used HLA DRB1*1501 class II tetramer-based cell sorted populations to show that specific CD4(+) T cells were able to recognize the peptide presented by HLA DR-matched keratinocytes. We observed that staphylococcal enterotoxin B (SEB) enhanced the IL-4 Der p 1-specific T cell response. This response was mediated by two synergistic mechanisms: first, SEB-induced IFN-gamma promoted class II and intercellular adhesion molecule-1 expression by presenting keratinocytes; and second, SEB-induced IL-4 directly amplified allergen-specific CD4(+) T cell production of many cytokines. We propose that handling of staphylococcal infection is a critical step in the amplification of the allergen-specific T cell response, linking two common disease associations and with implications for the prevention and treatment of atopic disease.
尽管临床和实验室证据支持葡萄球菌感染和环境过敏原在特应性皮炎发病机制中都发挥作用,但人体研究大多独立地考虑了这些变量。我们试图验证葡萄球菌超抗原影响过敏原特异性T细胞反应这一假说。我们首先绘制了Der p 1表位图谱,并使用基于HLA DRB1*1501 II类四聚体的细胞分选群体,以表明特定的CD4(+) T细胞能够识别由HLA DR匹配的角质形成细胞呈递的肽段。我们观察到葡萄球菌肠毒素B(SEB)增强了IL-4 Der p 1特异性T细胞反应。这种反应由两种协同机制介导:第一,SEB诱导的IFN-γ通过呈递角质形成细胞促进II类分子和细胞间黏附分子-1的表达;第二,SEB诱导的IL-4直接放大了过敏原特异性CD4(+) T细胞产生多种细胞因子的能力。我们提出,控制葡萄球菌感染是放大过敏原特异性T细胞反应的关键步骤,它将两种常见的疾病关联联系起来,并对特应性疾病的预防和治疗具有启示意义。