Zimmer K P, Poremba C, Weber P, Ciclitira P J, Harms E
University Children's Hospital, Münster, Germany.
Gut. 1995 May;36(5):703-9. doi: 10.1136/gut.36.5.703.
Coeliac disease is triggered by ingestion of wheat gliadin and is probably immune mediated. There is evidence by light microscopy that expression of class II major histocompatibility complex (MHC) molecules is increased in the small intestinal epithelium of patients with untreated coeliac disease and that gliadin can be taken up by small intestinal enterocytes. The pathway by which gliadin is transported to class II MHC proteins has not been demonstrated. Using an immunogold technique and thin frozen sections of jejunal biopsy specimens, gliadin, HLA-DR antigens, and IgA were localised at an ultrastructural level in the jejunal epithelium of patients with both untreated and treated coeliac disease and controls. Cathepsin D was used as a marker for late endosomes or lysosomes. The results show that gliadin is translocated into vacuoles positive for HLA-DR antigens as well as cathepsin D in jejunal enterocytes of patients with untreated coeliac disease. Secretory IgA may have a role in this translocation of gliadin, which is a specific event that occurred only in jejunal enterocytes from patients with untreated coeliac disease but not in a patient maintained on a gluten free diet or in controls. These results support a central role for epithelial cells of the human intestinal mucosa in the transport of gliadin to an HLA-DR positive compartment which precedes antigen presentation of gliadin to antigen sensitive T lymphocytes.
乳糜泻由摄入小麦醇溶蛋白引发，可能是免疫介导的。光学显微镜检查证据表明，未经治疗的乳糜泻患者小肠上皮中II类主要组织相容性复合体（MHC）分子的表达增加，且醇溶蛋白可被小肠肠上皮细胞摄取。醇溶蛋白转运至II类MHC蛋白的途径尚未得到证实。利用免疫金技术和空肠活检标本的薄冰冻切片，在未经治疗和经治疗的乳糜泻患者及对照者的空肠上皮中，在超微结构水平对醇溶蛋白、HLA - DR抗原和IgA进行了定位。组织蛋白酶D用作晚期内体或溶酶体的标志物。结果显示，在未经治疗的乳糜泻患者的空肠肠上皮细胞中，醇溶蛋白易位至对HLA - DR抗原以及组织蛋白酶D呈阳性的液泡中。分泌型IgA可能在醇溶蛋白的这种易位中起作用，这是一种仅在未经治疗的乳糜泻患者的空肠肠上皮细胞中发生的特异性事件，而在接受无麸质饮食的患者或对照者中未发生。这些结果支持人肠黏膜上皮细胞在将醇溶蛋白转运至HLA - DR阳性区室中起核心作用，该过程先于醇溶蛋白向抗原敏感T淋巴细胞的抗原呈递。
