Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis.
J Immunol
; 195(3): 832-40, 2015 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-26071562
ABSTRACT
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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MEDLINE
Assunto principal:
Vacinas contra Influenza
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Linfócitos T Reguladores
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Antígeno de Maturação de Linfócitos B
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Células Th17
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Esclerose Múltipla
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article