CD4+CD8+ human small intestinal T cells are decreased in celiac patients, with CD8 expression downregulated on intra-epithelial T cells in the active disease
CD4+CD8+ human small intestinal T cells are decreased in celiac patients, with CD8 expression downregulated on intra-epithelial T cells in the active disease
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DOI：
10.1097/00042737-200410000-00003
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发表时间：
2004-10-01
影响因子：
2.1
通讯作者：
O'Farrelly, C
中科院分区：
文献类型：
--
作者：
Carton, J;Byrne, B;O'Farrelly, C
背景/目的乳糜泻肠道病变被认为是由局部t淋巴细胞亚群失调引发和加剧的。本研究检查了腹腔患者肠道T细胞的变化，特别关注CD4(+)CD8(+) T细胞，免疫调节细胞，通常在小肠中发现的比例相对较高。方法采用螯合还原剂（上皮层）和胶原酶（固有层）处理，从活络性和治疗性乳糜泻患者的十二指肠活检组织中获得细胞。评估细胞产量和活力，流式细胞术分析检测CD4+CD8+ T细胞并定量CD8表达。结果令人惊讶的是，尽管肠细胞计数明显减少，但活动性乳糜泻患者上皮层的总t细胞产量并未增加，表现为浸润。在活动性乳糜泻患者中，CD4+CD8+ T细胞百分比在上皮层和固有层均显著降低。活动性乳糜泻患者上皮细胞CD4+CD8+ T细胞CD8表达水平显著降低。CD4+CD8+ T细胞比例在接受治疗的乳糜泻患者中没有恢复正常，其绒毛结构对谷蛋白戒断有反应。结论乳糜泻病变上皮内淋巴细胞未增加，可能需要我们重新考虑乳糜泻作为炎症性疾病的定义。治疗和未治疗的乳糜泻患者CD4（+）和CD8（+）水平低表明这些T细胞在遗传上易患乳糜泻的个体中固有地缺失。
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 CD4(+)CD8(+) T cells, immunoregulatory, cells normally found in relatively high proportions in the small intestine.Methods 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 CD4+CD8+ T cells and to quantify CD8 expression.Results 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, CD4+CD8+ T cell percentages were significantly decreased in both the epithelial layer and lamina propria. Levels of CD8 expression by CD4+CD8+ T cells in the epithelial layer were decreased significantly in patients with active coeliac disease. CD4+CD8+ T cell proportions did not return to normal in treated coeliac patients whose villous architecture had responded to gluten withdrawal.Conclusions 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 CD4(+)CD8(+) populations in treated as well as untreated coeliac patients indicate that these T cells are inherently absent in individuals genetically predisposed to coeliac disease.