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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/19149

Title: Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis
Authors: Dhaeze, Tessa
Peelen, Evelyn
Hombrouck, Anneleen
Peeters, Liesbet
Van Wijmeersch, Bart
Lemkens, Nele
Lemkens, Peter
Somers, Veerle
Lucas, Sophie
Broux, Bieke
Stinissen, Piet
Hellings, Niels
Issue Date: 2015
Citation: JOURNAL OF IMMUNOLOGY, 195 (3), p. 832-840
Abstract: Follicular regulatory T cells (T-FR) 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 T-FR are phenotypically distinct from tonsil-derived T-FR 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 T-FR is comparable with tonsil-derived T-FR. Moreover, we show that circulating T-FR 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 T-FR. MS patients had a significantly lower frequency of circulating T-FR compared with healthy control subjects. Furthermore, the circulating T-FR compartment of MS patients displayed an increased proportion of Th17-like T-FR. Finally, T-FR of MS patients had a strongly reduced suppressive function compared with healthy control subjects. We conclude that circulating T-FR are a circulating memory population derived from lymphoid resident T-FR, making them a valid alternative to investigate alterations in germinal center responses in the context of autoimmune diseases, and T-FR impairment is prominent in MS.
Notes: [Dhaeze, Tessa; Peelen, Evelyn; Peeters, Liesbet; Van Wijmeersch, Bart; Somers, Veerle; Broux, Bieke; Stinissen, Piet; Hellings, Niels] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Dhaeze, Tessa; Peelen, Evelyn; Peeters, Liesbet; Van Wijmeersch, Bart; Somers, Veerle; Broux, Bieke; Stinissen, Piet; Hellings, Niels] Transnat Univ Limburg, Sch Life Sci, B-3590 Diepenbeek, Belgium. [Hombrouck, Anneleen] Sci Inst Publ Hlth, Viral Dis Unit, Operat Direct Transmitted & Infect Dis, B-1200 Brussels, Belgium. [Van Wijmeersch, Bart] Rehabil & Multiple Sclerosis Ctr, B-3900 Overpelt, Belgium. [Lemkens, Nele; Lemkens, Peter] Hosp East Limburg, B-3600 Genk, Belgium. [Lucas, Sophie] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium.
URI: http://hdl.handle.net/1942/19149
DOI: 10.4049/jimmunol.1500759
ISI #: 000358070400013
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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