{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:04:53Z","timestamp":1790964293917,"version":"4.1.0"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,23]]},"abstract":"<jats:p>\n                    Immature T cells undergo a process of positive selection in the thymus when their new T cell receptor (TCR) engages and signals in response to self-peptides. As the T cell matures, a slew of negative regulatory molecules, including the inhibitory surface glycoprotein CD5, are up-regulated in proportion to the strength of the self-peptide signal. Together these regulators dampen TCR-proximal signaling and help avoid any subsequent peripheral activation of T cells by self-peptides. Paradoxically, antigen-specific T cells initially expressing more CD5 (CD5\n                    <jats:sup>hi<\/jats:sup>\n                    ) have been found to better persist as effector\/memory cells after a peripheral challenge. The molecular mechanisms underlying such a duality in CD5 function is not clear. We found that CD5 alters the basal activity of the NF-\u03baB signaling in resting peripheral T cells. When CD5 was conditionally ablated, T cells were unable to maintain higher expression of the cytoplasmic NF-\u03baB inhibitor I\u03baB\u03b1. Consistent with this, resting CD5\n                    <jats:sup>hi<\/jats:sup>\n                    T cells expressed more of the NF-\u03baB p65 protein than CD5\n                    <jats:sup>lo<\/jats:sup>\n                    cells, without significant increases in transcript levels, in the absence of TCR signals. This posttranslationally stabilized cellular NF-\u03baB depot potentially confers a survival advantage to CD5\n                    <jats:sup>hi<\/jats:sup>\n                    T cells over CD5\n                    <jats:sup>lo<\/jats:sup>\n                    ones. Taken together, these data suggest a two-step model whereby the strength of self-peptide\u2013induced TCR signal lead to the up-regulation of CD5, which subsequently maintains a proportional reserve of NF-\u03baB in peripheral T cells poised for responding to agonistic antigen-driven T cell activation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1922525117","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T20:35:08Z","timestamp":1591648508000},"page":"14342-14353","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["CD5 dynamically calibrates basal NF-\u03baB signaling in T cells during thymic development and peripheral activation"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-4986","authenticated-orcid":false,"given":"Courtney A.","family":"Matson","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seeyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Livak","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-2416","authenticated-orcid":false,"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apratim","family":"Mitra","sequence":"additional","affiliation":[{"name":"Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Love","sequence":"additional","affiliation":[{"name":"Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevil J.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/ncprheum0049","article-title":"Primer: Mechanisms of immunologic tolerance","volume":"2","author":"Singh N. 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