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• W2158410911 abstract "<h3>Objective</h3> Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease (CD) characterised by aberrant intraepithelial lymphocytes (IELs) of unknown origin that display an atypical CD3⁻CD7⁺icCD3⁺ phenotype. In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells. <h3>Design</h3> RCDII cell lines were compared with T-cell receptor positive (TCR⁺) IEL (T-IEL) lines by microarray analysis, real-time quantitative PCR and flow cytometry. This information was used to identify cells with an RCDII-associated phenotype in duodenal biopsies from non-refractory individuals by multicolour flow cytometry. <h3>Results</h3> RCDII lines were transcriptionally distinct from T-IEL lines and expressed higher levels of multiple natural killer (NK) cell receptors. In addition to the CD3⁻CD7⁺icCD3⁺ phenotype, the RCDII lines were distinguishable from other lymphocyte subsets by the absence of CD56, CD127 and CD34. Cells matching this surface lineage-negative (Lin⁻) CD7⁺CD127⁻CD34⁻ phenotype expressed a functional interleukin-15 (IL-15) receptor and constituted a significant proportion of IELs in duodenal specimens of patients without CD, particularly children, and were also found in the thymus. In patients without CD, the Lin⁻CD7⁺CD127⁻CD34⁻ subset was one of four subsets within the CD3⁻CD7⁺icCD3⁺ population that could be distinguished on the basis of differential expression of CD56 and/or CD127. <h3>Conclusion</h3> Our studies indicate that the CD3⁻CD7⁺icCD3⁺ population is heterogeneous and reveal the existence of a Lin⁻ subset that is distinct from T, B, NK and lymphoid tissue inducer cells. We speculate that this IL-15 responsive population represents the physiological counterpart of aberrant cells expanded in RCDII and transformed in RCDII-associated lymphoma." @default.
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• W2158410911 date "2012-07-03" @default.
• W2158410911 modified "2023-10-18" @default.
• W2158410911 title "Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II" @default.
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• W2158410911 doi "https://doi.org/10.1136/gutjnl-2012-302265" @default.
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