{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:51:33Z","timestamp":1789861893847,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,28]],"date-time":"2006-12-28T00:00:00Z","timestamp":1167264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA). Given that CD28\u2010null T cells are functionally heterogeneous, we undertook this study to screen for novel receptors on these cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy\u2010two patients with RA (ages 35\u201384 years) and 53 healthy persons (32 young controls ages 19\u201334 years, 21 older controls ages 39\u201386 years) were recruited. Phenotypes and proliferative capacity of T cells from fresh leukocytes and of long\u2010term cultures were monitored by flow cytometry. Lung biopsy specimens from patients with RA\u2010associated interstitial pneumonitis (IP) were examined by immunohistochemistry. Receptor functionality was assessed by crosslinking bioassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic stimulation of CD28+ T cells in vitro yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of leukocytes from patients with extraarticular RA showed a higher frequency of CD56+,CD28\u2010null T cells than in patients with disease confined to the joints or in healthy controls. CD56+,CD28\u2010null T cells had nil capacity for proliferation, consistent with cellular senescence. CD56+ T cells had skewed T cell receptor (TCR) \u03b1\/\u03b2\u2010chain usage and restricted TCR third complementarity\u2010determining region spectra. Histologic studies showed that CD56+ T cells were components of cellular infiltrates in RA\u2010associated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CD56\/TCR coligation induced higher production levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Chronic activation of T cells induces counterregulation of CD28 and CD56 expression. The loss of CD28 is accompanied by the gain of CD56 that confers TCR\u2010independent and TCR\u2010dependent activation pathways. We propose that accumulation of CD56+ T cells in RA contributes to maladaptive immune responses and that CD56+ T cells are potential targets for therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22310","type":"journal-article","created":{"date-parts":[[2006,12,28]],"date-time":"2006-12-28T23:49:54Z","timestamp":1167349794000},"page":"43-57","source":"Crossref","is-referenced-by-count":53,"title":["CD56\u2010expressing T cells that have features of senescence are expanded in rheumatoid arthritis"],"prefix":"10.1002","volume":"56","author":[{"given":"Joshua J.","family":"Michel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Turesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Lemster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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