IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis
Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, Inoges S, Lopez-Diaz de Cerio A, Palacios R, Sepulcre J, Moreno B, Gonzalez Z, Fernandez-Diez B, Melero I, Bendandi M, Villoslada P.
Department of Neurology, University of Navarra, Pamplona, Spain
Magazine: European Journal of Immunology
Date: Feb 1, 2008Immunology [SP] Cell Therapy Area [SP]
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.
CITATION Eur J Immunol. 2008 Feb;38(2):576-86
you maybe interested
The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.
The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.
Learn why we are different from other healthcare centers. Quality, speed, comfort and results.