IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis
Palabras clave : 
CD46
IL-10
MS
Stat-3
Tr1 cells Abbreviations: c(t): cycle threshold HC: healthy control MNE: mean normalized expression MS: multiple sclerosis Socs: suppressor of cytokine signaling Tr1 cell: T regulatory cell type 1 576 Ivan Martinez-Forero et al. Eur. J. Immunol. 2008. 38: 576–586 f 2008
Fecha incorporación: 
2008
Editorial : 
Wiley-Blackwell
ISSN: 
1521-4141
Cita: 
Martínez-Forero I, García-Muñoz R, Martínez-Pasamar S, Inoges S, López-Díaz de Cerio A, Palacios R, et al. IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 2008 Feb;38(2):576-586.
Resumen
T regulatory cells type 1 (Tr1 cells) are excellent candidates for cell therapy in multiple sclerosis (MS). The aim of our study was to assess the functional state of Tr1 cells and IL-10R signaling in patients with MS. Tr1 cells were induced in vitro by activation with anti-CD46 antibodies in controls and patients with MS. Cells were phenotyped by cytometry and suppression assays, and the expression of cytokines and transcription factors was evaluated by real-time PCR, ELISA, cytometry and Western blotting. We found that the activity of Tr1 cells and IL-10R signaling is impaired in MS patients since Tr1 cells isolated from MS patients produced less IL-10 than those obtained from controls. Indeed, the supernatants from Tr1 cells from controls did not suppress the proliferation of stimulated CD4(+) cells from patients with MS. Furthermore, the IL-10R signaling pathway was not fully active in CD4(+) cells from MS patients and these cells had higher baseline levels of SOCS3 transcripts than controls. Indeed, after in vitro IL-10 stimulation, the expression levels of the STAT1, STAT3 and IL-10RA genes were higher in MS patients than in controls. Moreover, Stat-3 phosphorylation was lower in controls than in patients after IL-10 stimulation. These results indicate that IL-10 regulatory function is impaired in patients with MS.

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