Carton Janet, Byrne Brendan, Madrigal-Estebas Laura, O'Donoghue Diarmuid P, O'Farrelly Cliona
Education and Research Centre, St Vincent's University Hospital, Dublin, Ireland.
Eur J Gastroenterol Hepatol. 2004 Oct;16(10):961-8. doi: 10.1097/00042737-200410000-00003.
BACKGROUND/OBJECTIVE: The intestinal lesion of coeliac disease is thought to be initiated and exacerbated by dysregulation of local T-lymphocyte sub-populations. This study examines changes in intestinal T cells from coeliac patients, with a particular focus on CD4CD8 T cells, immunoregulatory cells normally found in relatively high proportions in the small intestine.
Cells were obtained from duodenal biopsies from active and treated coeliac patients using chelating and reducing agents (epithelial layer) followed by collagenase treatment (lamina propria). Cell yield and viability were assessed and flow cytometric analysis was used to examine CD4CD8 T cells and to quantify CD8 expression.
Surprisingly, total T-cell yields in the epithelial layer did not increase in active coeliac disease although enterocyte counts decreased significantly, giving an appearance of infiltration. In active coeliac patients, CD4CD8 T cell percentages were significantly decreased in both the epithelial layer and lamina propria. Levels of CD8 expression by CD4CD8 T cells in the epithelial layer were decreased significantly in patients with active coeliac disease. CD4CD8 T cell proportions did not return to normal in treated coeliac patients whose villous architecture had responded to gluten withdrawal.
No increase of intra-epithelial lymphocytes in the coeliac lesion may require us to reconsider the definition of coeliac disease as an inflammatory condition. Low CD4CD8 populations in treated as well as untreated coeliac patients indicate that these T cells are inherently absent in individuals genetically predisposed to coeliac disease.
背景/目的:乳糜泻的肠道病变被认为是由局部T淋巴细胞亚群失调引发并加剧的。本研究检测了乳糜泻患者肠道T细胞的变化,特别关注CD4CD8 T细胞,这类免疫调节细胞通常在小肠中占比较高。
从活动期和经治疗的乳糜泻患者的十二指肠活检组织中获取细胞,先用螯合剂和还原剂处理(上皮层),随后用胶原酶处理(固有层)。评估细胞产量和活力,并采用流式细胞术分析检测CD4CD8 T细胞并定量CD8表达。
令人惊讶的是,尽管肠上皮细胞数量显著减少,呈现浸润现象,但活动期乳糜泻患者上皮层中的总T细胞产量并未增加。在活动期乳糜泻患者中,上皮层和固有层中的CD4CD8 T细胞百分比均显著降低。活动期乳糜泻患者上皮层中CD4CD8 T细胞的CD8表达水平显著降低。在绒毛结构对撤去麸质有反应的经治疗乳糜泻患者中,CD4CD8 T细胞比例并未恢复正常。
乳糜泻病变中上皮内淋巴细胞未增加可能需要我们重新考虑将乳糜泻定义为一种炎症性疾病。未经治疗和经治疗的乳糜泻患者中CD4CD8 T细胞数量均较低,这表明在遗传易患乳糜泻的个体中,这些T细胞天生就缺乏。