{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:30Z","timestamp":1791302490667,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Follicular regulatory T cells (TFR) have been extensively characterized in mice and participate in germinal center responses by regulating the maturation of B cells and production of (auto)antibodies. We report that circulating TFR are phenotypically distinct from tonsil-derived TFR in humans. They have a lower expression of follicular markers, and display a memory phenotype and lack of high expression of B cell lymphoma 6 and ICOS. However, the suppressive function, expression of regulatory markers, and FOXP3 methylation status of blood TFR is comparable with tonsil-derived TFR. Moreover, we show that circulating TFR frequencies increase after influenza vaccination and correlate with anti-flu Ab responses, indicating a fully functional population. Multiple sclerosis (MS) was used as a model for autoimmune disease to investigate alterations in circulating TFR. MS patients had a significantly lower frequency of circulating TFR compared with healthy control subjects. Furthermore, the circulating TFR compartment of MS patients displayed an increased proportion of Th17-like TFR. Finally, TFR of MS patients had a strongly reduced suppressive function compared with healthy control subjects. We conclude that circulating TFR are a circulating memory population derived from lymphoid resident TFR, making them a valid alternative to investigate alterations in germinal center responses in the context of autoimmune diseases, and TFR impairment is prominent in MS.<\/jats:p>","DOI":"10.4049\/jimmunol.1500759","type":"journal-article","created":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T03:40:47Z","timestamp":1434166847000},"page":"832-840","source":"Crossref","is-referenced-by-count":121,"title":["Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis"],"prefix":"10.1093","volume":"195","author":[{"given":"Tessa","family":"Dhaeze","sequence":"first","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Peelen","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneleen","family":"Hombrouck","sequence":"additional","affiliation":[{"name":"Viral Diseases Unit, Operational Direction of Transmitted and Infectious Diseases, Scientific Institute of Public Health , 1200 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbet","family":"Peeters","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"Rehabilitation and Multiple Sclerosis Center , 3900 Overpelt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nele","family":"Lemkens","sequence":"additional","affiliation":[{"name":"Hospital East-Limburg , 3600 Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lemkens","sequence":"additional","affiliation":[{"name":"Hospital East-Limburg , 3600 Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Somers","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lucas","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 Catholique de Louvain , 1200 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bieke","family":"Broux","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet","family":"Stinissen","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Hellings","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University , 3590 Diepenbeek ,","place":["Belgium"]},{"name":"School of Life Sciences, Transnational University Limburg , 3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703582963200_r1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1600-065X.2012.01122.x","article-title":"T cells that promote B-Cell maturation in systemic autoimmunity","volume":"247","author":"Weinstein","year":"2012","journal-title":"Immunol. 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