{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:11:38Z","timestamp":1793319098919,"version":"4.5.0"},"reference-count":50,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,5,30]]},"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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<jats:sup>\u2212<\/jats:sup>CD7<jats:sup>+<\/jats:sup>icCD3<jats:sup>+<\/jats:sup> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>RCDII cell lines were compared with T-cell receptor positive (TCR<jats:sup>+<\/jats:sup>) 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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<jats:sup>\u2212<\/jats:sup>CD7<jats:sup>+<\/jats:sup>icCD3<jats:sup>+<\/jats:sup> 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<jats:sup>\u2212<\/jats:sup>) CD7<jats:sup>+<\/jats:sup>CD127<jats:sup>\u2212<\/jats:sup>CD34<jats:sup>\u2212<\/jats:sup> 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<jats:sup>\u2212<\/jats:sup>CD7<jats:sup>+<\/jats:sup>CD127<jats:sup>\u2212<\/jats:sup>CD34<jats:sup>\u2212<\/jats:sup> subset was one of four subsets within the CD3<jats:sup>\u2212<\/jats:sup>CD7<jats:sup>+<\/jats:sup>icCD3<jats:sup>+<\/jats:sup> population that could be distinguished on the basis of differential expression of CD56 and\/or CD127.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our studies indicate that the CD3<jats:sup>\u2212<\/jats:sup>CD7<jats:sup>+<\/jats:sup>icCD3<jats:sup>+<\/jats:sup> population is heterogeneous and reveal the existence of a Lin<jats:sup>\u2212<\/jats:sup> 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gutjnl-2012-302265","type":"journal-article","created":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T17:23:09Z","timestamp":1341422589000},"page":"509-519","source":"Crossref","is-referenced-by-count":56,"title":["Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II"],"prefix":"10.1136","volume":"62","author":[{"given":"Frederike","family":"Schmitz","sequence":"first","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M L","family":"Tjon","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuching","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Leiden Genome Technology Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Kooy-Winkelaar","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J L F","family":"Lemmers","sequence":"additional","affiliation":[{"name":"Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein W","family":"Verspaget","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Luisa","family":"Mearin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J","family":"Staal","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco 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