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Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within V\u03b41 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans.<\/jats:p>","DOI":"10.1084\/jem.20150794","type":"journal-article","created":{"date-parts":[[2016,4,11]],"date-time":"2016-04-11T14:12:28Z","timestamp":1460383948000},"page":"841-857","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["CD1d-restricted peripheral T cell lymphoma in mice and humans"],"prefix":"10.1084","volume":"213","author":[{"given":"Emmanuel","family":"Bachy","sequence":"first","affiliation":[{"name":"CIRI, International Center for Infectiology Research, Universit\u00e9 de Lyon, 69007 Lyon, France 1"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1111, 69007 Lyon, France 2"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 69007 Lyon, France 3"},{"name":"Universit\u00e9 Lyon 1, Centre International de Recherche en Infectiologie, 69007 Lyon, France 4"},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR 5308, 69365 Lyon, France 5"},{"name":"Department of Hematology, Hospices Civils de Lyon, 69004 Lyon, France 6"},{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon1, 69007 Lyon, France 11"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Urb","sequence":"additional","affiliation":[{"name":"CIRI, International Center for Infectiology Research, Universit\u00e9 de Lyon, 69007 Lyon, France 1"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1111, 69007 Lyon, France 2"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 69007 Lyon, France 3"},{"name":"Universit\u00e9 Lyon 1, Centre International de Recherche en Infectiologie, 69007 Lyon, France 4"},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR 5308, 69365 Lyon, France 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Chandra","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037 12"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Robinot","sequence":"additional","affiliation":[{"name":"CIRI, International Center for Infectiology Research, Universit\u00e9 de Lyon, 69007 Lyon, France 1"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1111, 69007 Lyon, France 2"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 69007 Lyon, France 3"},{"name":"Universit\u00e9 Lyon 1, Centre International de Recherche en Infectiologie, 69007 Lyon, France 4"},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR 5308, 69365 Lyon, France 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Bricard","sequence":"additional","affiliation":[{"name":"CIRI, International Center for Infectiology Research, Universit\u00e9 de Lyon, 69007 Lyon, France 1"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1111, 69007 Lyon, France 2"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 69007 Lyon, France 3"},{"name":"Universit\u00e9 Lyon 1, Centre International de Recherche en Infectiologie, 69007 Lyon, France 4"},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR 5308, 69365 Lyon, France 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"de Bernard","sequence":"additional","affiliation":[{"name":"AltraBio SAS, 69007 Lyon, France 13"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Traverse-Glehen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospices Civils de Lyon, 69004 Lyon, France 7"},{"name":"CNRS, UMR 5239, 69342 Lyon, France 14"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Gazzo","sequence":"additional","affiliation":[{"name":"Department of Cytogenetics, Hospices Civils de Lyon, 69004 Lyon, France 8"},{"name":"CNRS, UMR 5239, 69342 Lyon, France 14"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Blond","sequence":"additional","affiliation":[{"name":"Institut Albert Bonniot, INSERM U823, Universit\u00e9 J. 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