{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:18:03Z","timestamp":1784852283919,"version":"3.55.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of \u03b3\u03b4 T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, V\u03b39+V\u03b42+ (V\u03b39+) T cells, in JIA. We found that as opposed to CD4+ T cells, equally high percentages (\u223c35%) of V\u03b39+ T cells in SF and peripheral blood (PB) produced TNF-\u03b1 and IFN-\u03b3. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for V\u03b39J\u03b31.2+ T cells, similarly amplified cytokine secretion by SF and PB V\u03b39+ T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF &amp;gt; PB V\u03b39+ T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although V\u03b39+ T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4+CD25+FOXP3+ cells (regulatory T cells). Furthermore, coculture with the V\u03b39+ T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial V\u03b39+ T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.1102403","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T04:34:27Z","timestamp":1332822867000},"page":"4349-4359","source":"Crossref","is-referenced-by-count":32,"title":["Cellular Interactions of Synovial Fluid \u03b3\u03b4 T Cells in Juvenile Idiopathic Arthritis"],"prefix":"10.1093","volume":"188","author":[{"given":"Anna","family":"Bendersky","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Marcu-Malina","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yackov","family":"Berkun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Gerstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meital","family":"Nagar","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itamar","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Padeh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Bank","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]},{"name":"Department of Medicine, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University , Ramat Gan 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,5,1]]},"reference":[{"key":"2025032410044057700_r1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/322179a0","article-title":"A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes","volume":"322","author":"Bank","year":"1986","journal-title":"Nature"},{"key":"2025032410044057700_r2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/322145a0","article-title":"Identification of a putative second T-cell receptor","volume":"322","author":"Brenner","year":"1986","journal-title":"Nature"},{"key":"2025032410044057700_r3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/1074-7613(95)90178-7","article-title":"Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells","volume":"3","author":"Morita","year":"1995","journal-title":"Immunity"},{"key":"2025032410044057700_r4","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1146\/annurev.immunol.18.1.975","article-title":"[gamma][delta] cells: a right time and a right place for a conserved third way of protection","volume":"18","author":"Hayday","year":"2000","journal-title":"Annu. 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