Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy

M. Chiarini, F. Serana, C. Zanotti, R. Capra, S. Rasia, M. Rottoli, M. Rovaris, D. Caputo, G. Cavaletti, M. Frigo, B. Frigeni, R. Clerici, M. Rezzonico, L. Caimi, L. Imberti

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.Conclusions: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalMultiple Sclerosis Journal
Volume18
Issue number6
DOIs
Publication statusPublished - 2012

Fingerprint

Interferon-beta
Regulatory T-Lymphocytes
Multiple Sclerosis
Interleukin-10
RNA
Therapeutics
Population
T-Lymphocyte Subsets
Real-Time Polymerase Chain Reaction
Blood Cells
Flow Cytometry
Biomarkers
Monoclonal Antibodies
T-Lymphocytes
Phenotype

Keywords

  • CD46
  • interferon-beta
  • interleukin-10
  • multiple sclerosis
  • MxA
  • regulatory T cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy. / Chiarini, M.; Serana, F.; Zanotti, C.; Capra, R.; Rasia, S.; Rottoli, M.; Rovaris, M.; Caputo, D.; Cavaletti, G.; Frigo, M.; Frigeni, B.; Clerici, R.; Rezzonico, M.; Caimi, L.; Imberti, L.

In: Multiple Sclerosis Journal, Vol. 18, No. 6, 2012, p. 788-798.

Research output: Contribution to journalArticle

Chiarini, M, Serana, F, Zanotti, C, Capra, R, Rasia, S, Rottoli, M, Rovaris, M, Caputo, D, Cavaletti, G, Frigo, M, Frigeni, B, Clerici, R, Rezzonico, M, Caimi, L & Imberti, L 2012, 'Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy', Multiple Sclerosis Journal, vol. 18, no. 6, pp. 788-798. https://doi.org/10.1177/1352458511427720
Chiarini, M. ; Serana, F. ; Zanotti, C. ; Capra, R. ; Rasia, S. ; Rottoli, M. ; Rovaris, M. ; Caputo, D. ; Cavaletti, G. ; Frigo, M. ; Frigeni, B. ; Clerici, R. ; Rezzonico, M. ; Caimi, L. ; Imberti, L. / Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy. In: Multiple Sclerosis Journal. 2012 ; Vol. 18, No. 6. pp. 788-798.
@article{5c6a6e28931640aab85dbf9231cbcd7f,
title = "Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy",
abstract = "Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.Conclusions: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.",
keywords = "CD46, interferon-beta, interleukin-10, multiple sclerosis, MxA, regulatory T cells",
author = "M. Chiarini and F. Serana and C. Zanotti and R. Capra and S. Rasia and M. Rottoli and M. Rovaris and D. Caputo and G. Cavaletti and M. Frigo and B. Frigeni and R. Clerici and M. Rezzonico and L. Caimi and L. Imberti",
year = "2012",
doi = "10.1177/1352458511427720",
language = "English",
volume = "18",
pages = "788--798",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "6",

}

TY - JOUR

T1 - Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy

AU - Chiarini, M.

AU - Serana, F.

AU - Zanotti, C.

AU - Capra, R.

AU - Rasia, S.

AU - Rottoli, M.

AU - Rovaris, M.

AU - Caputo, D.

AU - Cavaletti, G.

AU - Frigo, M.

AU - Frigeni, B.

AU - Clerici, R.

AU - Rezzonico, M.

AU - Caimi, L.

AU - Imberti, L.

PY - 2012

Y1 - 2012

N2 - Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.Conclusions: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

AB - Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.Conclusions: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

KW - CD46

KW - interferon-beta

KW - interleukin-10

KW - multiple sclerosis

KW - MxA

KW - regulatory T cells

UR - http://www.scopus.com/inward/record.url?scp=84861827392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861827392&partnerID=8YFLogxK

U2 - 10.1177/1352458511427720

DO - 10.1177/1352458511427720

M3 - Article

C2 - 22086901

AN - SCOPUS:84861827392

VL - 18

SP - 788

EP - 798

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 6

ER -