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IL‐10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis

2008; Wiley; Volume: 38; Issue: 2 Linguagem: Inglês

10.1002/eji.200737271

1521-4141

Iván Martínez‐Forero, Ricardo García-Muñóz, Sara Martinez‐Pasamar, Susana Inogès, Ascensión López‐Díaz de Cerio, Ricardo Palácios, Jorge Sepulcre, Beatriz Moreno, Zaira Gonzalez, Begoña Fernández-Díez, Ignacio Melero, Maurizio Bendandi, Pablo Villoslada,

Multiple Sclerosis Research Studies

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.