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Available evidence indicates that they may derive from CD8+ T cells, but most published data have been obtained using cells that bear an invariant transgenic T cell receptor that recognizes an Ag that is not present in normal mice. Here, we have used complementary fate mapping and adoptive transfer experiments to identify the cellular lineage of origin of DNT cells in wild-type mice with a polyclonal T cell repertoire. We show that TCR-\u03b1\/\u03b2+ DNT cells can be traced back to CD8+ and CD4+CD8+ double positive cells in the thymus. We also demonstrate that polyclonal DNT cells generated in secondary lymphoid organs proliferate upon adoptive transfer and can regain CD8 expression in lymphopenic environment. These results demonstrate the cellular origin of DNT cells and provide a conceptual framework to understand their presence in pathological circumstances.<\/jats:p>","DOI":"10.1002\/jlb.1ab0120-548r","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T03:08:06Z","timestamp":1581563286000},"page":"851-857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["TCR-\u03b1\/\u03b2 CD4\u2212 CD8\u2212 double negative T cells arise from CD8+ T cells"],"prefix":"10.1093","volume":"108","author":[{"given":"No\u00e9","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , USA"},{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Flores-Mendoza","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokratis A","family":"Apostolidis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Rosetti","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-3621","authenticated-orcid":true,"given":"Jos\u00e9 C","family":"Crisp\u00edn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , USA"},{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City , Mexico"},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey , Mexico City , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"2023032108071196400_jlb10575-cit-0001","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nri1257","article-title":"T-cell development made simple","volume":"4","author":"Z\u00fa\u00f1iga-Pfl\u00fccker","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"2023032108071196400_jlb10575-cit-0002","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.autrev.2018.02.001","article-title":"TCR\u03b1\u03b2+CD3+CD4\u2212CD8\u2212 HedrichCM. (double negative) T cells in autoimmunity","volume":"17","author":"Brandt","year":"2018","journal-title":"Autoimmunity Rev"},{"key":"2023032108071196400_jlb10575-cit-0003","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.immuni.2018.03.009","article-title":"Unconventional T cell targets for cancer immunotherapy","volume":"48","author":"Godfrey","year":"2018","journal-title":"Immunity"},{"key":"2023032108071196400_jlb10575-cit-0004","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/77513","article-title":"Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression","volume":"6","author":"Zhang","year":"2000","journal-title":"Nat Med"},{"key":"2023032108071196400_jlb10575-cit-0005","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S0031-3955(05)70272-8","article-title":"Autoimmune lymphoproliferative syndrome. 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