{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:43:09Z","timestamp":1791164589206,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>To investigate whether impaired extrathymic T cell maturation and\/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT \u03b1-chain (preT\u03b1) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In controls, the RAG1-1A\/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR\n                      <jats:sup>+<\/jats:sup>\n                      ) and immature (CD2\n                      <jats:sup>+<\/jats:sup>\n                      CD7\n                      <jats:sup>+<\/jats:sup>\n                      TCR\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) IELs (\u223c8 mRNA copies\/18S rRNA U). PreT\u03b1 was expressed almost exclusively in CD2\n                      <jats:sup>+<\/jats:sup>\n                      CD7\n                      <jats:sup>+<\/jats:sup>\n                      TCR\n                      <jats:sup>\u2212<\/jats:sup>\n                      IELs (\u223c40 mRNA copies\/18S rRNA U). By contrast, RAG1 and preT\u03b1 mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values &lt;0.01 for mature and &lt;0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p&lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gut.2007.125526","type":"journal-article","created":{"date-parts":[[2008,2,25]],"date-time":"2008-02-25T20:44:22Z","timestamp":1203972262000},"page":"189-195","source":"Crossref","is-referenced-by-count":8,"title":["Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?"],"prefix":"10.1136","volume":"58","author":[{"given":"A","family":"Bas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Forsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Sj\u00f6berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Hernell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-L","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,2,25]]},"reference":[{"key":"2025120519174659000_58.2.189.1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2003.00017.x"},{"key":"2025120519174659000_58.2.189.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri885"},{"key":"2025120519174659000_58.2.189.3","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230231"},{"key":"2025120519174659000_58.2.189.4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.5.2719"},{"key":"2025120519174659000_58.2.189.5","doi-asserted-by":"publisher","DOI":"10.1136\/gut.37.6.766"},{"key":"2025120519174659000_58.2.189.6","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.9.1473"},{"key":"2025120519174659000_58.2.189.7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01461.x"},{"key":"2025120519174659000_58.2.189.8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00948.x"},{"key":"2025120519174659000_58.2.189.9","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.2.208"},{"key":"2025120519174659000_58.2.189.10","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1203\/00006450-199012000-00005","article-title":"Intestinal \u03b3\/\u03b4 receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. 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