Maiuri L, Picarelli A, Boirivant M, Coletta S, Mazzilli M C, De Vincenzi M, Londei M, Auricchio S
Children's Hospital Pausilipon, Naples, Italy.
Gastroenterology. 1996 May;110(5):1368-78. doi: 10.1053/gast.1996.v110.pm8613040.
BACKGROUND & AIMS: Mucosal cell-mediated immune response is considered the central event in the pathogenesis of celiac disease. In cultured intestinal explants from celiacs in remission, we have characterized the early stages of gliadin-induced immune activation.
Intestinal biopsy specimens (15 treated celiacs and 13 controls) were cultured with gliadin or maize prolamine digests for 24 hours as well as for 1, 2, 4, 6, 8, and 12 hours in some subjects. The expression of immunologic markers was detected by immunocytochemistry.
Gliadin challenge may initiate two parallel pathways, one of which leads to T-cell activation and another that precedes it. Epithelial cells overexpress DR molecules after 1 hour, and in a second stage T lymphocytes become fully activated. Moreover, T lymphocytes migrate in the upper mucosal layers. T lymphocytes that migrate in the higher lamina propria compartments are mainly CD4+ and show markers of activation; migrating intraepithelial lymphocytes are CD8+ and do not express these markers.
In vitro gliadin challenge is a suitable model to reproduce various immunologic features of celiac lesions; these may be caused by different pathways. The comprehension of these phenomena is essential to clarify the distinctive pathogenic mechanisms leading to disease and may help in defining novel therapeutic approaches.
黏膜细胞介导的免疫反应被认为是乳糜泻发病机制中的核心事件。在来自缓解期乳糜泻患者的培养肠外植体中，我们已经对麦醇溶蛋白诱导的免疫激活的早期阶段进行了特征描述。
将肠道活检标本（15例接受治疗的乳糜泻患者和13例对照）与麦醇溶蛋白或玉米醇溶蛋白消化物一起培养24小时，部分受试者还培养1、2、4、6、8和12小时。通过免疫细胞化学检测免疫标志物的表达。
麦醇溶蛋白激发可能启动两条平行途径，其中一条导致T细胞激活，另一条先于它发生。上皮细胞在1小时后过度表达DR分子，在第二阶段T淋巴细胞完全激活。此外，T淋巴细胞迁移到黏膜上层。在固有层较高区域迁移的T淋巴细胞主要是CD4 + 并显示激活标志物；迁移的上皮内淋巴细胞是CD8 + 且不表达这些标志物。
体外麦醇溶蛋白激发是重现乳糜泻病变各种免疫特征的合适模型；这些可能由不同途径引起。理解这些现象对于阐明导致疾病的独特致病机制至关重要，并且可能有助于确定新的治疗方法。
