Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients

• Published in: Immunology 2009-07, Vol.127 (3), p.418-428
• Main Authors: Frisullo, Giovanni, Nociti, Viviana, Iorio, Raffaele, Patanella, Agata K, Caggiula, Marcella, Marti, Alessandro, Sancricca, Cristina, Angelucci, Francesco, Mirabella, Massimiliano, Tonali, Pietro A, Batocchi, Anna P
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cell Proliferation; Cells, Cultured; Coculture Techniques; Female; Forkhead Transcription Factors - metabolism; Humans; Immune Tolerance; Interleukin-2 Receptor alpha Subunit - blood; Male; Multiple Sclerosis, Relapsing-Remitting - immunology; T-Box Domain Proteins - blood; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Up-Regulation - immunology; Young Adult
• ISSN: 1365-2567
• DOI: 10.1111/j.1365-2567.2008.02963.x

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.