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Aberrant intraepithelial lymphocytes (IELs) are the key feature of refractory coeliac disease type II (RCDII), but the cellular origin of these aberrant IELs remains unclear. In a recent paper Schmitz et al1 further explored previously characterised aberrant IEL cell lines from four patients with RCDII by using a broad spectrum of cell specific markers, RNA array and immunological techniques, to compare these cell lines to IELs from the fetal intestine, the intestine of children and adults and the thymus.
IELs are a heterogeneous population of lymphocytes with innate and adaptive features that inhabit the small and large intestine. IELs are important for the maintenance of tolerance to common food antigens versus defence against pathogens. The development and expansion of IELs is influenced by nutritional factors, mainly vitamins and their active metabolites such as retinoic acid, and phytochemicals such as ligands of the aryl hydrocarbon receptor from cruciferous vegetables.2 However, uncontrolled activation and expansion of IELs leading to mucosal damage and potentially malignancy, is part of pathological response of chronic inflammatory conditions, especially of coeliac disease (CD).
Up to 5% of CD patients, particularly those diagnosed over the age of 50, fail to recover from clinical symptoms and villous atrophy despite strict avoidance of dietary gluten.3 After exclusion of dietary transgression and other potential underlying diseases,4 patients can be diagnosed with RCD which is classically classified as type I or type II, based on the histological coexpression of CD3 and CD8 (RCDI) or absence of such coexpression (RCDII), respectively.5 Moreover, in RCDII CD3 is largely expressed intracellularly (icCD3). Additional tools to diagnose RCDII …
Contributors Both authors contributed equally.
Funding VZ and DS declare no conflicting interests. DS receives funding from the European Union, the State of Rhino-Palatinate and the German Ministry of Research and Development.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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