Dynamics of Non-conventional Intraepithelial Lymphocytes-NK, NKT, and γδ T-in Celiac Disease: Relationship with Age, Diet, and Histopathology
Dynamics of Non-conventional Intraepithelial Lymphocytes-NK, NKT, and γδ T-in Celiac Disease: Relationship with Age, Diet, and Histopathology
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DOI：
10.1007/s10620-010-1534-5
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发表时间：
2011-07-01
影响因子：
3.1
通讯作者：
Ruiz de Morales, Jose G.
中科院分区：
文献类型：
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作者：
Calleja, Sara;Vivas, Santiago;Ruiz de Morales, Jose G.
上皮内淋巴细胞（IEL）是一种在乳糜泻（CD）中产生的异质性淋巴细胞群，其在CD发病机制中的作用尚不明确，为了研究诊断年龄、饮食和组织学病变的严重程度如何与非常规IEL人群中观察到的变化相关，前瞻性分析了101例确诊的乳糜泻患者，包括66例诊断时（45例儿童，21例成人）和112例非乳糜泻对照（12例儿童，100例成人）。采用六色流式细胞术对十二指肠活检组织的IEL进行了研究。分析了年龄、饮食、营养状况等因素对实验结果的影响（麸质摄入量）和组织病理学与相应的年龄对照相比，儿童和成人患者均显示十二指肠上皮内淋巴细胞增多症，在每个非常规IEL人群中具有显著差异：CD3+ TCR γ δ、NK（CD3-、CD16+、CD56+）、NKT（CD3+、CD161+、CD56+）和iNKT（CD3+ V α 24）（均P < 0.001）。麸质摄入不仅与严重萎缩直接相关，而且与NK（P = 0.02）、NKT（P = 0.003）和iNKT（P = 0.03）百分比降低相关。与成人乳糜泻患者相比，乳糜泻儿童iNKT和γ δ IEL的变化更为显著（分别为P = 0.02和0.01）。与此相反，增加的CD 3 + TCR γ δ是饮食和Marsh等级independent.The典型的表型配置文件的上皮内淋巴细胞增多症在未经治疗的小儿和成人腹腔包括增加的CD 3 + TCR γ δ人口减少NK，NKT，和iNKT细胞。NK、NKT和iNKT IEL是与饮食、年龄和组织病理学相关的动态人群，而γ δ IEL则不是。
Intraepithelial lymphocytes (IEL) are a heterogeneous population of lymphocytes raised in celiac disease (CD), whose role in CD pathogenesis remains to be defined.To investigate how the age of diagnosis, diet, and the severity of the histological lesions are related to the changes observed in unconventional IEL populations.Prospective analysis of 101 confirmed celiac patients from a single center, including 66 at diagnosis (45 children, 21 adults) and 112 non-celiac controls (12 children, 100 adults). IEL from duodenal biopsies were studied by six-color flow cytometry. The results were analyzed in relationship with age, diet (gluten intake), and histopathology (Marsh type).In comparison with respective age controls, both children and adult patients showed duodenal intraepithelial lymphocytosis with significant differences in every single non-conventional IEL population: CD3+ TCR gamma delta, NK (CD3-, CD16+, CD56+), NKT (CD3+, CD161+, CD56+), and iNKT (CD3+ V alpha 24) (P < 0.001 for all). Gluten intake was not only directly associated with severe atrophy, but also with decreased percentages of NK (P = 0.02), NKT (P = 0.003), and iNKT (P = 0.03). Changes in iNKT and gamma delta IEL were more marked in celiac children compared with celiac adults (P = 0.02 and 0.01, respectively). In contrast, increased CD3+ TCR gamma delta were diet- and Marsh grade-independent.The typical phenotypical profile of intraepithelial lymphocytosis in untreated pediatric and adult celiacs consists of increased CD3+ TCR gamma delta populations with decreased NK, NKT, and iNKT cells. NK, NKT, and iNKT IEL, but not gamma delta IEL, are dynamic populations associated with diet, age, and histopathology.