{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T23:43:18Z","timestamp":1794526998351,"version":"4.9.1"},"reference-count":41,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"unspecified","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016239","name":"University of Occupational and Environmental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016239","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,2,10]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Various immune-cell subsets intricately mediate the pathogenesis of systemic lupus erythematosus (SLE). However, the role of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in SLE remains unclear. We investigated the proportions and characteristics of peripheral CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and their association with clinical manifestations of SLE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively enrolled 211 patients with SLE and 48 age- and sex-matched healthy controls (HCs). Peripheral CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were analysed using flow cytometry. The primary endpoint was the comparison of peripheral CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell subset characteristics between patients and HCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with SLE (mean age, 42.3 years; women, 89% and mean disease duration, 112.8 months) had significantly higher proportions of na\u00efve CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells (CCR7\n                      <jats:sup>+<\/jats:sup>\n                      CD45RA\n                      <jats:sup>+<\/jats:sup>\n                      ), CD8\n                      <jats:sup>+<\/jats:sup>\n                      terminally differentiated effector memory cells (CCR7\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD45RA\n                      <jats:sup>+<\/jats:sup>\n                      ) and activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells (CD38\n                      <jats:sup>+<\/jats:sup>\n                      HLA-DR\n                      <jats:sup>+<\/jats:sup>\n                      ) in peripheral blood mononuclear cells than HCs (p&lt;0.001). Activated CD8\n                      <jats:bold>\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:bold>\n                      T cells produced granzyme B and interferon-\u03b3, which correlated with serum double-stranded (ds) DNA antibodies (rs=0.3146, p&lt;0.0001) and 50% haemolytic unit of complement (rs=\u22120.3215, p=0.0003), and were significantly increased in patients with active systemic, renal or haematological involvement (p&lt;0.05). Cluster analysis-based subgroup classification based on CD8 cell differentiation and activation revealed a group with high numbers of activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, highly active SLE and organ damage, including active nephritis and persistently high cell counts after a 24-week treatment, indicating treatment resistance (high anti-dsDNA antibody titres and high glucocorticoid doses).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In SLE, greater proportions of highly cytotoxic and proinflammatory activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in peripheral blood-modulated disease activity, organ damage and residual treatment resistance, presenting a potential treatment target.\n                    <\/jats:p>\n                  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