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Regulatory T cells fail to suppress CD4 + T‐bet + T cells in relapsing multiple sclerosis patients
Author(s) -
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.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02963.x
Subject(s) - foxp3 , il 2 receptor , multiple sclerosis , immunology , regulatory t cell , interleukin 21 , pathogenesis , t cell , microbiology and biotechnology , biology , immune system , medicine , endocrinology
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.