Bernardo David, van Hoogstraten Ingrid M W, Verbeek Wieke H M, Peña A Salvador, Mearin M Luisa, Arranz Eduardo, Garrote José Antonio, Scheper Rik J, Schreurs Marco W J, Bontkes Hetty J, Mulder Chris J J, von Blomberg B Mary E
Mucosal Immunology Lab, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain.
Clin Immunol. 2008 Feb;126(2):172-9. doi: 10.1016/j.clim.2007.09.005. Epub 2007 Oct 31.
A small proportion of coeliac disease (CD) patients become refractory (RCD) to a gluten-free diet (GFD) showing uncontrolled immune-mediated enteropathy. Some of these patients exhibit a high risk to develop enteropathy-associated T-cell lymphoma (EATL).
The aim of the study was to find whether a lack of circulating homeostatic T cells, such as Treg, Tgammadelta(+) or iNKT cells would be associated with the development of RCD or EATL.
We investigated in a total of 137 CD patients [28 untreated, 80 responsive to GFD and 29 RCD (14 type I and 15 type II)] and 73 age-matched healthy volunteers the frequency of Treg, Tgammadelta(+) and iNKT lymphocytes by flow cytometric analysis of peripheral blood.
Circulating Tgammadelta(+) cell and Treg frequencies in RCD were comparable to those in healthy controls. However, RCD patients had significantly reduced numbers of circulating iNKT cells, as compared to age-matched patients responding to a GFD. This reduction was similar in RCD patients with and without aberrant intraepithelial lymphocytes and in patients with EATL. Circulating iNKT cell numbers were not reduced in untreated coeliac patients. GFD treated patients had a significantly increased proportion of CD4(+) iNKT cells.
Follow-up studies are necessary to determine whether CD4(+) iNKT cells control the immune response against gluten and their absence contributes to the progression to RCD and EATL.
一小部分乳糜泻（CD）患者对无麸质饮食（GFD）产生耐药性（RCD），表现为免疫介导的肠病失控。其中一些患者发生肠病相关T细胞淋巴瘤（EATL）的风险较高。
本研究旨在探讨循环中稳态T细胞（如调节性T细胞、γδ(+)T细胞或不变自然杀伤T细胞）的缺乏是否与RCD或EATL的发生有关。
我们通过对外周血进行流式细胞术分析，调查了总共137例CD患者[28例未治疗、80例对GFD有反应和29例RCD（14例I型和15例II型）]以及73名年龄匹配的健康志愿者中调节性T细胞、γδ(+)T细胞和不变自然杀伤T淋巴细胞的频率。
RCD患者循环中的γδ(+)T细胞和调节性T细胞频率与健康对照相当。然而，与年龄匹配的对GFD有反应的患者相比，RCD患者循环中的不变自然杀伤T细胞数量显著减少。在有和没有异常上皮内淋巴细胞的RCD患者以及EATL患者中，这种减少情况相似。未治疗的乳糜泻患者循环中的不变自然杀伤T细胞数量没有减少。接受GFD治疗的患者中CD4(+)不变自然杀伤T细胞的比例显著增加。
需要进行后续研究以确定CD4(+)不变自然杀伤T细胞是否控制针对麸质的免疫反应，以及它们的缺失是否导致疾病进展为RCD和EATL。
