Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis.
(2015) Journal of Immunology — Vol. 195, n° 3, p. 832-840 (2015)
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- 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.
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Dhaeze, T., Peelen, E., Hombrouck, A., Peeters, L., Van Wijmeersch, B., Lemkens, N., Lemkens, P., Somers, V., Lucas, S., Broux, B., Stinissen, P., & Hellings, N. (2015). Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis. Journal of Immunology, 195(3), 832-840. https://doi.org/10.4049/jimmunol.1500759 (Original work published 2015)