{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:30Z","timestamp":1790965350697,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T00:00:00Z","timestamp":1112832000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatism"],"published-print":{"date-parts":[[2005,4]]},"abstract":"Abstract<\/jats:title>Objective<\/jats:title>To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).<\/jats:p><\/jats:sec>Methods<\/jats:title>Mice of the MRL\/Mp strain were studied as a polygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25\u2212 CD4+ T cells were cultured independently or together in the presence of anti\u2010CD3\/CD28 monoclonal antibody\u2013coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine.<\/jats:p><\/jats:sec>Results<\/jats:title>While MRL\/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25\u2212 T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL\/Mp CD4+,CD25\u2212 T cells were cultured with H\u20102\u2013matched CBA\/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20976","type":"journal-article","created":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T15:22:23Z","timestamp":1112887343000},"page":"1180-1184","source":"Crossref","is-referenced-by-count":99,"title":["MRL\/Mp CD4+,CD25\u2212 T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: A novel defect of T cell regulation in systemic lupus erythematosus"],"prefix":"10.1002","volume":"52","author":[{"given":"C. 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