Hall R P, Smith A D, Streilein R D
Department of Medicine, Duke University Medical Center and Durham VA Hospital, North Carolina 27710, USA.
Dig Dis Sci. 2000 Oct;45(10):2036-43. doi: 10.1023/a:1005512513007.
Dermatitis herpetiformis (DH) and isolated gluten-sensitive enteropathy (GSE) are gluten-sensitive diseases in which ingestion of dietary gluten results in the development of clinical disease. Patients with DH develop cutaneous IgA deposits and a severe skin disease, but rarely develop gastrointestinal symptoms. Patients with isolated GSE develop clinically significant gastrointestinal symptoms, but not skin disease or cutaneous IgA deposits. The aim of this study was to investigate the mechanism by which a mucosal immune response to the same dietary antigen can result in two distinct clinical phenotypes. T-cell lines were derived from activated T-cells in the small bowel mucosa of five patients with DH and 14 patients with isolated GSE and analyzed for T-cell markers and cytokine production in vitro. T-cell lines from DH and isolated GSE patients produced IFN-gamma after stimulation (mean: DH = 2,619 pg/ml; isolated GSE = 1,993 pg/ml; NS). T-cell lines from patients with DH, however, produced significantly more IL-4 than the T-cell lines from patients with isolated GSE (IL-4: DH = 2,010 pg/ml; isolated GSE = 235 pg/ml; P < 0.05). Analysis of intracytoplasmic cytokine production by the T-cell lines showed that T-cell lines from patients with DH were CD4+ predominant, with a greater proportion of CD4+/IL4+ cells than CD4+/IFN-gamma+ cells. In contrast, isolated GSE T-cell lines were predominantly CD8+, with an equal proportion of IL-4- and IFN-gamma-positive cells. These studies demonstrate that T cell lines from patients with DH produce significantly more IL-4 than T-cell lines from patients with isolated GSE, while producing similar amounts of IFN-gamma. This difference in cytokine pattern may play an important role in the different clinical manifestations of these two forms of gluten sensitivity.
疱疹样皮炎（DH）和孤立性麸质敏感性肠病（GSE）是麸质敏感性疾病，摄入膳食麸质会导致临床疾病的发生。DH患者会出现皮肤IgA沉积和严重的皮肤疾病，但很少出现胃肠道症状。孤立性GSE患者会出现具有临床意义的胃肠道症状，但无皮肤疾病或皮肤IgA沉积。本研究的目的是探讨对同一膳食抗原的黏膜免疫反应可导致两种不同临床表型的机制。从5例DH患者和14例孤立性GSE患者的小肠黏膜活化T细胞中获得T细胞系，并在体外分析其T细胞标志物和细胞因子产生情况。DH和孤立性GSE患者的T细胞系在刺激后产生γ干扰素（平均值：DH = 2,619 pg/ml；孤立性GSE = 1,993 pg/ml；无显著性差异）。然而，DH患者的T细胞系产生的白细胞介素-4显著多于孤立性GSE患者的T细胞系（白细胞介素-4：DH = 2,010 pg/ml；孤立性GSE = 235 pg/ml；P < 0.05）。对T细胞系细胞内细胞因子产生情况的分析表明，DH患者的T细胞系以CD4+为主，CD4+/白细胞介素-4+细胞的比例高于CD4+/γ干扰素+细胞。相比之下，孤立性GSE的T细胞系主要为CD8+，白细胞介素-4阳性细胞和γ干扰素阳性细胞的比例相等。这些研究表明，DH患者的T细胞系产生的白细胞介素-4显著多于孤立性GSE患者的T细胞系，而γ干扰素的产生量相似。这种细胞因子模式的差异可能在这两种麸质敏感性形式的不同临床表现中起重要作用。
