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The lack of cytotoxicity may result from impaired lineage commitment of CTL in the absence of CD8, or diminished competitiveness during selection against (unimpaired) development of CD4<jats:sup>+<\/jats:sup> T cells on MHC class II (MHC II). To differentiate between these possibilities, we have generated a double\u2010knockout mouse (MHC II<jats:sup>\u2013\/\u2013<\/jats:sup>CD8\u03b1<jats:sup>\u2013\/\u2013<\/jats:sup>). In MHC II<jats:sup>\u2013\/\u2013<\/jats:sup>CD8\u03b1<jats:sup>\u2013\/\u2013<\/jats:sup> mice, developing MHC class I (MHC I)\u2010reactive thymocytes cannot rely upon CD8 for selection, but they also cannot be overwhelmed by efficient selection of MHC II\u2010reactive thymocytes. In this mouse, a large, heterogeneous population of peripheral coreceptor double\u2010negative (DN) and CD4<jats:sup>+<\/jats:sup> T cells develops. Peripheral DN T cells are fully functional CTL. They display cytolytic activity against allogeneic MHC, and against syngeneic MHC following lymphocytic choriomeningitis virus (LCMV) infection. Cells from LCMV\u2010infected mice bind more MHC I tetramer at lower concentrations than their wild\u2010type CTL counterparts. These results demonstrate unequivocally that CD8 is not required for commitment of thymocytes to the CTL lineage.<\/jats:p>","DOI":"10.1002\/eji.200737710","type":"journal-article","created":{"date-parts":[[2008,5,8]],"date-time":"2008-05-08T15:33:04Z","timestamp":1210260784000},"page":"1511-1521","source":"Crossref","is-referenced-by-count":7,"title":["Rescue of cytotoxic function in the CD8\u03b1 knockout mouse by removal of MHC class II"],"prefix":"10.1002","volume":"38","author":[{"given":"David\u2004S.","family":"Riddle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u2004J.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin\u2004G.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas\u2004B.","family":"Kepler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Maile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey\u2004A.","family":"Frelinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward\u2004J.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,20]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/341746a0"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/342559a0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/335229a0"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90169-4"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.02.003"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri798"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(86)90139-8"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90462-8"},{"key":"e_1_2_8_9_2","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.4049\/jimmunol.155.8.3727","article-title":"T cell development in CD8\u2013\/\u2013 mice. 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