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人食管上皮细胞的抗原呈递和 MHC Ⅱ类分子表达:在嗜酸性食管炎中的作用。

Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

机构信息

Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.

出版信息

Am J Pathol. 2011 Feb;178(2):744-53. doi: 10.1016/j.ajpath.2010.10.027.

Abstract

Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis.

摘要

专业抗原呈递细胞 (APC) 在启动免疫反应中发挥着关键作用。在病理条件下,黏膜表面的上皮细胞作为非专业 APC,从而调节暴露部位的免疫反应。食管上皮细胞通过在主要组织相容性复合体 (MHC) Ⅱ类上呈递抗原,可能有助于嗜酸性食管炎 (EoE) 的发病机制。我们的目标是证明食管上皮细胞在 MHC Ⅱ类系统上加工和呈递抗原的能力,并研究上皮细胞抗原呈递对 EoE 的贡献。免疫组织化学检测到 HLA-DR、CD80 和 CD86 的表达,酶联免疫吸附试验检测到食管活检中的干扰素-γ (IFNγ)。通过逆转录酶 PCR、流式细胞术和共聚焦显微镜研究了人食管上皮细胞系 HET-1A 的抗原呈递。通过流式细胞术和 IL-2 分泌评估 T 辅助淋巴细胞增殖。EoE 患者的黏膜中 IFNγ 和 MHC Ⅱ类增加。IFNγ增加了 HET-1A 细胞中 HLA-DP、HLA-DQ、HLA-DR 和 CIITA 的 mRNA。HET-1A 吞噬细胞碎片并加工卵白蛋白。IFNγ 处理后,HET-1A 细胞表达 HLA-DR。HET-1A 刺激 T 辅助细胞活化。在这项研究中,我们证明了食管上皮细胞在 IFNγ 存在下作为非专业 APC 的能力。食管上皮细胞抗原呈递可能有助于嗜酸性食管炎的病理生理学。

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