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Simultaneous quantification of natural and inducible regulatory T-cell subsets during interferon-β therapy of multiple sclerosis patients

BACKGROUND: The mechanisms underlying the therapeutic activity of interferon-β in multiple sclerosis are still not completely understood. In the present study, we evaluated the short and long-term effects of interferon-β treatment on different subsets of regulatory T cells in relapsing–remitting mul...

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Detalles Bibliográficos
Autores principales: Chiarini, Marco, Capra, Ruggero, Serana, Federico, Bertoli, Diego, Sottini, Alessandra, Giustini, Viviana, Scarpazza, Cristina, Rovaris, Marco, Torri Clerici, Valentina, Ferraro, Diana, Galgani, Simonetta, Solaro, Claudio, Conti, Marta Zaffira, Visconti, Andrea, Imberti, Luisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161224/
https://www.ncbi.nlm.nih.gov/pubmed/32299447
http://dx.doi.org/10.1186/s12967-020-02329-5
Descripción
Sumario:BACKGROUND: The mechanisms underlying the therapeutic activity of interferon-β in multiple sclerosis are still not completely understood. In the present study, we evaluated the short and long-term effects of interferon-β treatment on different subsets of regulatory T cells in relapsing–remitting multiple sclerosis patients biologically responsive to treatment because of mixovirus resistance protein A inducibility. METHODS: In this prospective longitudinal study, subsets of natural regulatory T cells (naïve, central memory and effector memory) and inducible regulatory T cells (Tr1), as well as in vitro-induced regulatory T cells (Tr1-like cells), were simultaneously quantified by flow cytometry in samples prepared from 148 therapy-naïve multiple sclerosis patients obtained before and after 6, 12, 18, and 24 months of interferon-β-1a treatment. mRNA for interleukin-10 and Tr1-related genes (CD18, CD49b, and CD46, together with Cyt-1 and Cyt-2 CD46-associated isoforms) were quantified in Tr1-like cells. RESULTS: Despite profound inter-individual variations in the modulation of all regulatory T-cell subsets, the percentage of natural regulatory T cells increased after 6, 12, and 24 months of interferon-β treatment. This increase was characterized by the expansion of central and effector memory regulatory T-cell subsets. The percentage of Tr1 significantly enhanced at 12 months of therapy and continued to be high at the subsequent evaluation points. Patients experiencing relapses displayed a higher percentage of naïve regulatory T cells and a lower percentage of central memory regulatory T cells and of Tr1 before starting interferon-β therapy. In addition, an increase over time of central memory and of Tr1 was observed only in patients with stable disease. However, in vitro-induced Tr1-like cells, prepared from patients treated for 24 months, produced less amount of interleukin-10 mRNA compared with pre-treatment Tr1-like cells. CONCLUSION: Interferon-β induces the expansion of T regulatory subsets endowed with a high suppressive activity, especially in clinically stable patients. The overall concurrent modulation of natural and inducible regulatory T-cell subsets might explain the therapeutic effects of interferon-β in multiple sclerosis patients.