Regulatory T cells fail to suppress CD4+T-bet+ T cells in relapsing multiple sclerosis patients

Giovanni Frisullo, Viviana Nociti, Raffaele Iorio, Agata K. Patanella, Marcella Caggiula, Alessandro Marti, Cristina Sancricca, Francesco Angelucci, Massimiliano Mirabella, Pietro A. Tonali, Anna P. Batocchi

Research output: Contribution to journalArticlepeer-review

Abstract

Summary Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system and a defect in the regulatory T-cell subset seems to be involved in the pathogenesis of the disease. Foxp3 is a transcription factor that is selectively expressed in CD4+ CD25 + regulatory T cells and is required for their development and function. T-bet is a key transcription factor for the development of T helper 1 (Th1) cells. We found that both the percentage of circulating CD4+ CD25+ Foxp3+ cells and Foxp3 expression were lower in relapsing-remitting (RR) MS patients during relapses than during remission. Otherwise, the percentage of CD4+ T-bet+ T cells and T-bet expression in CD4+ T cells were higher in relapsing than in remitting RRMS patients. CD4+ CD25+ T cells both from relapsing and from remitting RRMS patients showed significantly less capacity than corresponding cells from healthy subjects to suppress autologous CD4 + CD25- T-cell proliferation, despite a similar Foxp3 expression level. CD4+ CD25+ T cells from healthy subjects and patients in remission clearly reduced T-bet mean fluorescence intensity (MFI) in CD4+ CD25- T cells up to a ratio of 1:10, whereas CD4+ CD25+ T cells from patients in relapse were able to reduce T-bet expression only at a high ratio. Our data indicate that the increased number of regulatory T (T-reg) cells and the increased Foxp3 expression in circulating CD4+ CD25+ T cells may contribute to the maintenance of tolerance in the remission phase of MS. Moreover, the inhibitory capacity of CD4+ CD25+ T cells seems to be impaired in relapsing patients under inflammatory conditions, as shown by the high levels of T-bet expression in CD4+T cells.

Original languageEnglish
Pages (from-to)418-428
Number of pages11
JournalImmunology
Volume127
Issue number3
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Foxp3
  • Multiple sclerosis
  • Relapse
  • Remission
  • T-bet

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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