{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:35:23Z","timestamp":1791300923678,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T00:00:00Z","timestamp":1416873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MPI R21"],"award-info":[{"award-number":["MPI R21"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double negative (DN) \u03b1\u03b2 T cells are legitimate components of the normal immune system. However, they are poorly understood and largely ignored by immunologists because of their historical association with the lymphoproliferation that occurs in mice (\n                    <jats:italic>lpr<\/jats:italic>\n                    and\n                    <jats:italic>gld<\/jats:italic>\n                    ) and humans (autoimmune lymphoproliferative syndromes patients) with impaired Fas\u2010mediated apoptosis where they are considered abnormal T cells. We believe that the traditional view that DN T cells that cause lymphoproliferation (hereafter referred to as\n                    <jats:italic>lpr<\/jats:italic>\n                    DN T cells) are CD4 and CD8 T cells that lost their coreceptor, conceived more than two decades ago, is flawed and that conflating\n                    <jats:italic>lpr<\/jats:italic>\n                    DN T cells with DN T cells found in normal immune system (hereafter referred to as nDN T cells) is unnecessarily dampening interest of this potentially important cell type. To begin rectifying these misperceptions, we will revisit the traditional view of\n                    <jats:italic>lpr<\/jats:italic>\n                    DN T cells and show that it does not hold true in light of recent immunological advances. In lieu of it, we offer a new model proposing that Fas\u2010mediated apoptosis actively removes normally existing DN T cells from the periphery and that impaired Fas\u2010mediated apoptosis leads to accumulation of these cells rather than\n                    <jats:italic>de novo<\/jats:italic>\n                    generation of DN T cells from activated CD4 or CD8 T cells. By doing so, we hope to provoke a new discussion that may lead to a consensus about the origin of\n                    <jats:italic>lpr<\/jats:italic>\n                    DN T cells and regulation of their homeostasis by the Fas pathway and reignite wider interest in nDN T cells.\n                  <\/jats:p>","DOI":"10.1038\/icb.2014.99","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T05:36:26Z","timestamp":1416893786000},"page":"305-310","source":"Crossref","is-referenced-by-count":76,"title":["Double Negative (DN) \u03b1\u03b2 T Cells: misperception and overdue recognition"],"prefix":"10.1111","volume":"93","author":[{"given":"Maria N","family":"Martina","sequence":"first","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Medicine, Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Rabb","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel Rahim A","family":"Hamad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Medicine, Johns Hopkins University School of Medicine  Baltimore MD 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