{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:47:45Z","timestamp":1788223665589,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007253","name":"Nancy E. 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Because of recent evidence that loss of CD28 cells is typical of terminally differentiated lymphocytes, the aim of this study was to examine functional subsets of CD8+ T cells in patients with JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood and\/or waste synovial fluid samples were collected from children with a definite diagnosis of JIA (n = 98). Deidentified peripheral blood (n = 33) and cord blood (n = 13) samples from healthy donors were also collected. CD8+ and CD4+ T cells were screened for novel receptors, and where indicated, bioassays were performed to determine the functional relevance of the identified receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>JIA patients had a naive T cell compartment with shortened telomeres, and their entire T cell pool had reduced proliferative capacity. They had an overabundance of CD31+CD28<jats:sup>null<\/jats:sup>CD8+ T cells, which was a significant feature of oligoarticular JIA (n = 62) as compared to polyarticular JIA (n = 36). CD31+ CD28<jats:sup>null<\/jats:sup>CD8+ T cells had limited mitotic capacity and expressed high levels of the senescence antigens histone \u03b3H2AX and\/or p16. Ligation of CD31, which was independent of the T cell receptor (TCR), sufficiently induced tyrosine phosphorylation, vesicle exocytosis, and production of interferon\u2010\u03b3 and interleukin\u201010.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data provide the first evidence of cell senescence, as represented by CD31+CD28<jats:sup>null<\/jats:sup> CD8+ T cells, in the pathophysiology of JIA. Activation of these unusual cells in a TCR\u2010independent manner suggests that they are maladaptive and could be potential targets for immunotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38015","type":"journal-article","created":{"date-parts":[[2013,5,17]],"date-time":"2013-05-17T19:08:53Z","timestamp":1368817733000},"page":"2201-2210","source":"Crossref","is-referenced-by-count":37,"title":["Premature Cell Senescence and T Cell Receptor\u2013Independent Activation of CD8+ T Cells in Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Jeffrey A.","family":"Dvergsten","sequence":"first","affiliation":[{"name":"Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine Pittsburgh 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