{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:33:17Z","timestamp":1790775197455,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,5,31]],"date-time":"2008-05-31T00:00:00Z","timestamp":1212192000000},"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":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Previous studies have shown that the suppressive capacity of CD4+,CD25++ T cells is compromised in patients with rheumatoid arthritis (RA) and restored by anti\u2013tumor necrosis factor \u03b1 (anti\u2010TNF\u03b1) therapy. Given the lack of specific cell surface markers for human Treg cells, this study aimed to define surface markers for identifying and enriching Treg cells with enhanced regulatory ability within the CD4+,CD25++ T cell compartment and to provide additional understanding of the effects of anti\u2010TNF\u03b1 antibodies in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of membrane\u2010bound TNF\u03b1 in human peripheral blood CD4+ T cells was analyzed by flow cytometry in healthy individuals and RA patients before and after anti\u2010TNF\u03b1 treatment. Membrane\u2010bound TNF\u03b1\u2010positive and TNF\u03b1\u2010negative CD4+,CD25++ T cells were purified by fluorescence\u2010activated cell sorting, and their suppressive capacity was assessed in vitro by a standard suppression assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A substantial number of CD4+,CD25++ T cells expressed membrane\u2010bound TNF\u03b1. Membrane\u2010bound TNF\u03b1\u2010positive CD4+,CD25++ T cells displayed reduced antiinflammatory cytokine production and less potent suppressor capacity, since 4 times more cells were required to achieve 50% inhibition compared with their membrane\u2010bound TNF\u03b1\u2010negative counterparts. Treatment of RA patients with TNF\u03b1\u2010specific antibodies led to a reduction in the number of membrane\u2010bound TNF\u03b1\u2010positive CD4+,CD25++ T cells from peripheral blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicate that the absence of membrane\u2010bound TNF\u03b1 on CD4+,CD25++ T cells can be used to characterize and enrich for Treg cells with maximal suppressor potency. Enrichment of membrane\u2010bound TNF\u03b1\u2010negative CD4+,CD25+ cells in the CD4+,CD25++ T cell compartment may contribute to restoring the compromised suppressive ability of CD4+,CD25++ T cell populations in RA patients after anti\u2010TNF\u03b1 treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23460","type":"journal-article","created":{"date-parts":[[2008,5,31]],"date-time":"2008-05-31T21:18:22Z","timestamp":1212268702000},"page":"1609-1618","source":"Crossref","is-referenced-by-count":25,"title":["Suppressor activity among CD4+,CD25++ T cells is discriminated by membrane\u2010bound tumor necrosis factor \u03b1"],"prefix":"10.1002","volume":"58","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"van Dongen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Ulrich","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. 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