Simultaneous quantification of natural and inducible regulatory T-cell subsets during interferon-ß therapy of multiple sclerosis patients.
J Transl Med
; 18(1): 169, 2020 04 16.
Article
en En
| MEDLINE
| ID: mdl-32299447
ABSTRACT
BACKGROUND:
The mechanisms underlying the therapeutic activity of interferon-ß in multiple sclerosis are still not completely understood. In the present study, we evaluated the short and long-term effects of interferon-ß 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-ß-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-ß 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-ß 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-ß 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-ß in multiple sclerosis patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esclerosis Múltiple Recurrente-Remitente
/
Esclerosis Múltiple
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Transl Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia