{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:14:47Z","timestamp":1790284487999,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2007,9,7]],"date-time":"2007-09-07T00:00:00Z","timestamp":1189123200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2007,9,7]],"date-time":"2007-09-07T00:00:00Z","timestamp":1189123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Expanded populations of CD4<jats:sup>+<\/jats:sup> T cells lacking the co-stimulatory molecule CD28 (CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells in peripheral blood have previously been associated with extra-articular manifestations and human cytomegalovirus (HCMV) infection, but their presence in and contribution to joint manifestations is not clear. In the present article we investigated the distribution of CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells in the synovial membrane, synovial fluid and peripheral blood of RA patients, and analysed the association with erosive disease and anti-citrullinated protein antibodies. CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-V\u03b2 subsets of CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells in peripheral blood were often absent in synovial fluid. CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells in blood and synovial fluid showed specificity for HCMV antigens, and their presence was clearly associated with HCMV seropositivity but not with anti-citrullinated protein antibodies in the serum or synovial fluid, nor with erosive disease. Together these data imply a primary role for CD4<jats:sup>+<\/jats:sup>CD28<jats:sup>null<\/jats:sup> T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis.<\/jats:p>","DOI":"10.1186\/ar2286","type":"journal-article","created":{"date-parts":[[2007,9,7]],"date-time":"2007-09-07T18:13:27Z","timestamp":1189188807000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Skewed distribution of proinflammatory CD4+CD28nullT cells in rheumatoid arthritis"],"prefix":"10.1186","volume":"9","author":[{"given":"Andreas ER","family":"Fasth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omri","family":"Snir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna AT","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Nordmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsar","family":"Rahbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"af Klint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas K","family":"Bj\u00f6rkstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kristin","family":"Ulfgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald F","family":"van Vollenhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianne","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Trollmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,9,7]]},"reference":[{"key":"2137_CR1","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/ar2107","volume":"9","author":"SK Lundy","year":"2007","unstructured":"Lundy SK, Sarkar S, Tesmer LA, Fox DA: Cells of the synovium in rheumatoid arthritis. 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