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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 3/2014

Open Access 01-06-2014 | Research article

Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis

Authors: Hélène Asnagli, Delphine Martire, Nathalie Belmonte, Julie Quentin, Hervé Bastian, Mathilde Boucard-Jourdin, Papa Babacar Fall, Anne-Laure Mausset-Bonnefont, Amélie Mantello-Moreau, Sandrine Rouquier, Irène Marchetti, Christian Jorgensen, Arnaud Foussat, Pascale Louis-Plence

Published in: Arthritis Research & Therapy | Issue 3/2014

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Abstract

Introduction

Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for the development of therapies designed to suppress inflammation in an antigen-specific manner. Type 1 regulatory T (Tr1) cells are defined by their capacity to produce high levels of interleukin 10 (IL-10), which contributes to their ability to suppress pathological immune responses in several settings. The aim of this study was to evaluate the therapeutic potential of collagen type II–specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice.

Methods

Col-Treg clones were isolated and expanded from collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibody– and collagen-induced arthritis models. The in vivo suppressive mechanism of Col-Treg clones on effector T-cell proliferation was also investigated.

Results

Col-Treg clones are characterized by their specific cytokine profile (IL-10highIL-4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and granzyme B. A single infusion of Col-Treg cells reduced the incidence and clinical symptoms of arthritis in both preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific Tr1 cells decreased the proliferation of antigen-specific effector T cells in vivo significantly.

Conclusions

Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients whose disease is refractory to current treatments.
Appendix
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Metadata
Title
Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis
Authors
Hélène Asnagli
Delphine Martire
Nathalie Belmonte
Julie Quentin
Hervé Bastian
Mathilde Boucard-Jourdin
Papa Babacar Fall
Anne-Laure Mausset-Bonnefont
Amélie Mantello-Moreau
Sandrine Rouquier
Irène Marchetti
Christian Jorgensen
Arnaud Foussat
Pascale Louis-Plence
Publication date
01-06-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4567

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