Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice
Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice
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DOI：
10.1189/jlb.1106653
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Rothenberg, Marc E.
中科院分区：
文献类型：
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作者：
Mishra, Anil;Schlotman, James;Rothenberg, Marc E.
我们之前已经建立了一种过敏原诱导的嗜酸性食管炎(EE)的小鼠模型，其特征是上皮内嗜酸性粒细胞、细胞外颗粒沉积和上皮细胞增殖，其特征模拟了不同形式的EE个体观察到的病理生理变化。我们现在检验适应性T细胞免疫在启动实验性EE中起关键作用的假设。我们首先证明EE的诱导与食道中淋巴细胞亚群(B+、CD4(+)和CD8(+)细胞)的增加有关。我们通过鼻内变应原致敏的方法，在野生型和各种淋巴细胞亚群缺陷小鼠中诱导了实验性EE。通过抗主要碱性蛋白和抗增殖细胞核抗原免疫组织化学方法检测嗜酸性粒细胞水平和上皮细胞增殖情况。RAG1基因缺陷小鼠的食道嗜酸性粒细胞聚集被完全消融，但没有发现B细胞或抗原特异性抗体的作用，因为B细胞缺陷(IgH6)小鼠的实验性EE没有减弱。此外，T细胞缺陷(叉头盒N1-/-)小鼠被保护免受实验性EE的诱导。CD8α基因缺陷的小鼠发育成未改变的实验性EE，而CD4基因缺陷的小鼠仅受到适度保护，不受疾病诱导。综上所述，这些研究表明了CD4(+)和CD4(-)细胞群在EE发病机制中的作用，并证明实验性过敏原诱导的EE依赖于适应性T细胞免疫。
We have previously developed a murine model of allergen-induced eosinophilic esophagitis (EE), characterized by intraepithelial eosinophils, extracellular granule deposition, and epithelial cell hyperplasia, features that mimic the pathophysiological changes observed in individuals with various forms of EE. We now test the hypothesis that adaptive T cell immunity is critical in initiating experimental EE. We first demonstrate that EE induction is associated with an increase in lymphocyte subpopulations (B+, CD4(+), and CD8(+) cells) in the esophagus. We induced experimental EE in wild-type and various lymphocyte subpopulation-deficient mice by intranasal allergen sensitization. Eosinophil levels and epithelial cell proliferation were determined by performing antimajor basic protein and antiproliferation cell nuclear antigen immunohistochemical analysis. Eosinophil accumulation in the esophagus was ablated completely in RAG1 gene-deficient mice, but no role for B cells or antigen-specific antibodies was found, as B cell-deficient (IgH6) mice developed unabated, experimental EE. In addition, T cell-deficient (forkhead box N1-/-) mice were protected from the induction of experimental EE. CD8 alpha-deficient mice developed unaltered, experimental EE, and CD4-deficient mice were only protected moderately from disease induction. Taken together, these studies indicate a role for CD4(+) and CD4(-) cell populations in EE pathogenesis and demonstrate that experimental allergen-induced EE is dependent on adaptive T cell immunity.