{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:28:16Z","timestamp":1784824096889,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006315","name":"ReumaNL (Dutch Arthritis Foundation)","doi-asserted-by":"publisher","award":["17-2-403"],"award-info":[{"award-number":["17-2-403"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is an autoimmune disease characterised by B cell hyperactivity. CXCR5+ follicular helper T cells (Tfh), CXCR5-PD-1hi peripheral helper T cells (Tph) and CCR9+ Tfh-like cells have been implicated in driving B cell hyperactivity in pSS; however, their potential overlap has not been evaluated. Our aim was to study the overlap between the two CXCR5- cell subsets and to study their PD-1\/ICOS expression compared to \u201ctrue\u201d CXCR5\/PD-1\/ICOS-expressing Tfh cells. CXCR5- Tph and CCR9+ Tfh-like cell populations from peripheral blood mononuclear cells of pSS patients and healthy controls (HC) were compared using flow cytometry. PD-1\/ICOS expression from these cell subsets was compared to each other and to CXCR5+ Tfh cells, taking into account their differentiation status. CXCR5- Tph cells and CCR9+ Tfh-like cells, both in pSS patients and HC, showed limited overlap. PD-1\/ICOS expression was higher in memory cells expressing CXCR5 or CCR9. However, the highest expression was found in CXCR5\/CCR9 co-expressing T cells, which are enriched in the circulation of pSS patients. CXCR5- Tph and CCR9+ Tfh-like cells are two distinct cell populations that both are enriched in pSS patients and can drive B cell hyperactivity in pSS. The known upregulated expression of CCL25 and CXCL13, ligands of CCR9 and CXCR5, at pSS inflammatory sites suggests concerted action to facilitate the migration of CXCR5+CCR9+ T cells, which are characterised by the highest frequencies of PD-1\/ICOS-positive cells. Hence, these co-expressing effector T cells may significantly contribute to the ongoing immune responses in pSS.<\/jats:p>","DOI":"10.3390\/ijms241511952","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:27:46Z","timestamp":1690421266000},"page":"11952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["CCR9\/CXCR5 Co-Expressing CD4 T Cells Are Increased in Primary Sj\u00f6gren\u2019s Syndrome and Are Enriched in PD-1\/ICOS-Expressing Effector T Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5329-5787","authenticated-orcid":false,"given":"Anneline C.","family":"Hinrichs","sequence":"first","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aike A.","family":"Kruize","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris P. J. G.","family":"Lafeber","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen L.","family":"Leavis","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5571-2324","authenticated-orcid":false,"given":"Joel A. G.","family":"van Roon","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0140-6736(05)66990-5","article-title":"Sjogren\u2019s syndrome","volume":"366","author":"Fox","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16047","DOI":"10.1038\/nrdp.2016.47","article-title":"Sjogren syndrome","volume":"2","author":"Baldini","year":"2016","journal-title":"Nat. Rev. Dis. 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