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Subsets of these cell types can lack both CD4 and CD8 coreceptor expression. Beyond these known subsets, we identify CD4\u2212CD8\u2212TCR\u03b1\u03b2+, double-negative (DN) T cells, in mouse secondary lymphoid organs. DN T cells are a unique unconventional thymic-derived T cell subset. In contrast to CD5high DN thymocytes that preferentially yield TCR\u03b1\u03b2+ CD8\u03b1\u03b1 intestinal lymphocytes, we find that mature CD5low DN thymocytes are precursors to peripheral DN T cells. Using reporter mouse strains, we show that DN T cells transit through the immature CD4+CD8+ (double-positive) thymocyte stage. Moreover, we provide evidence that DN T cells can differentiate in MHC-deficient mice. Our study demonstrates that MHC-independent thymic selection can yield DN T cells that are distinct from NKT, \u03b3\u03b4 T, mucosal-associated invariant T, and CD8\u03b1\u03b1 T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.2000156","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T21:25:23Z","timestamp":1590009923000},"page":"133-142","source":"Crossref","is-referenced-by-count":10,"title":["MHC-Independent Thymic Selection of CD4 and CD8 Coreceptor Negative \u03b1\u03b2 T Cells"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4776-8696","authenticated-orcid":false,"given":"Roxanne","family":"Collin","sequence":"first","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-4382","authenticated-orcid":false,"given":"F\u00e9lix","family":"Lombard-Vadnais","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]},{"name":"Department of Microbiology and Immunology, McGill University, Montreal , Quebec H3A 0G4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E","family":"Hillhouse","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-4810","authenticated-orcid":false,"given":"Marie-\u00c8ve","family":"Lebel","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Chabot-Roy","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J","family":"Melichar","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec H3T 1J4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-2795","authenticated-orcid":false,"given":"Sylvie","family":"Lesage","sequence":"additional","affiliation":[{"name":"Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4 ,","place":["Canada"]},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"2025030417503988500_r1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/icb.2010.119","article-title":"Molecular and genetic parameters defining T-cell clonal selection","volume":"89","author":"Labrecque","year":"2011","journal-title":"Immunol. 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