{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:12:55Z","timestamp":1790784775717,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In refractory celiac disease (RCD), intestinal epithelial damage persists despite a gluten-free diet. Characteristic for RCD type II (RCD II) is the presence of aberrant surface TCR-CD3\u2212 intraepithelial lymphocytes (IELs) that can progressively replace normal IELs and eventually give rise to overt lymphoma. Therefore, RCD II is considered a malignant condition that forms an intermediate stage between celiac disease (CD) and overt lymphoma. We demonstrate in this study that surface TCR-CD3\u2212 IEL lines isolated from three RCD II patients preferentially lyse epithelial cell lines. FACS analysis revealed that DNAM-1 was strongly expressed on the three RCD cell lines, whereas other activating NK cell receptors were not expressed on all three RCD cell lines. Consistent with this finding, cytotoxicity of the RCD cell lines was mediated mainly by DNAM-1 with only a minor role for other activating NK cell receptors. Furthermore, enterocytes isolated from duodenal biopsies expressed DNAM-1 ligands and were lysed by the RCD cell lines ex vivo. Although DNAM-1 on CD8+ T cells and NK cells is known to mediate lysis of tumor cells, this study provides, to our knowledge, the first evidence that (pre)malignant cells themselves can acquire the ability to lyse epithelial cells via DNAM-1. This study confirms previous work on epithelial lysis by RCD cell lines and identifies a novel mechanism that potentially contributes to the gluten-independent tissue damage in RCD II and RCD-associated lymphoma.<\/jats:p>","DOI":"10.4049\/jimmunol.1003382","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T02:57:54Z","timestamp":1303959474000},"page":"6304-6312","source":"Crossref","is-referenced-by-count":23,"title":["DNAM-1 Mediates Epithelial Cell-Specific Cytotoxicity of Aberrant Intraepithelial Lymphocyte Lines from Refractory Celiac Disease Type II Patients"],"prefix":"10.1093","volume":"186","author":[{"given":"Jennifer M-L","family":"Tjon","sequence":"first","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M C","family":"Kooy-Winkelaar","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greetje J","family":"Tack","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Free University Medical Center , 1081 HV, Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Mieke","family":"Mommaas","sequence":"additional","affiliation":[{"name":"Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco W J","family":"Schreurs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Free University Medical Center , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco W","family":"Schilham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Free University Medical Center , 1081 HV, Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"van Bergen","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,6,1]]},"reference":[{"key":"2025032411285078200_r1","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1136\/gut.2006.114512","article-title":"Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience","volume":"56","author":"Al-Toma","year":"2007","journal-title":"Gut"},{"key":"2025032411285078200_r2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.bpg.2005.02.001","article-title":"Refractory coeliac disease","volume":"19","author":"Daum","year":"2005","journal-title":"Best Pract. 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