{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:52:19Z","timestamp":1785372739015,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate peripheral lymphopenia, a frequent finding in primary Sj\u00f6gren\u2019s syndrome (pSS) associated with higher disease activity and increased mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Prospective, cross-sectional study of consecutive patients with pSS (n\u2009=\u200966) and healthy controls (n\u2009=\u2009181). Lymphocyte subsets were analysed by flow cytometry, na\u00efve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated \u03b2-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In pSS, lymphopenia mainly affected na\u00efve CD4+ T cells. We noted a lower frequency of proliferating na\u00efve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, na\u00efve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of na\u00efve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In pSS, evidence for increased proliferation of na\u00efve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of na\u00efve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/rheumatology\/keaa105","type":"journal-article","created":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T04:46:05Z","timestamp":1583037965000},"page":"588-597","source":"Crossref","is-referenced-by-count":43,"title":["Lymphopenia in primary Sj\u00f6gren\u2019s syndrome is associated with premature aging of na\u00efve CD4+ T cells"],"prefix":"10.1093","volume":"60","author":[{"given":"Johannes","family":"Fessler","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical University of Graz, Graz, Austria"},{"name":"Department of Neurology, Harvard Medical School, Brigham and Women\u2019s Hospital, Harvard, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Fasching","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schwinger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H","family":"Stradner","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"2021020119073182300_keaa105-B1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nrrheum.2013.110","article-title":"Advances in understanding the pathogenesis of primary Sj\u00f6gren\u2019s syndrome","volume":"9","author":"Nocturne","year":"2013","journal-title":"Nat Rev 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