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

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 interleuki...

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Bibliographic Details
Published in:Arthritis research & therapy 2014-05, Vol.16 (3), p.R115-R115
Main Authors: Asnagli, Hélène, Martire, Delphine, Belmonte, Nathalie, Quentin, Julie, Bastian, Hervé, Boucard-Jourdin, Mathilde, Fall, Papa Babacar, Mausset-Bonnefont, Anne-Laure, Mantello-Moreau, Amélie, Rouquier, Sandrine, Marchetti, Irène, Jorgensen, Christian, Foussat, Arnaud, Louis-Plence, Pascale
Format: Article
Language:English
Subjects:
Adoptive Transfer - methods
Analysis
Animals
Arthritis
Arthritis, Experimental - immunology
Arthritis, Experimental - therapy
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - therapy
Care and treatment
Cell Proliferation
Cells, Cultured
Collagen
Collagen Type II - immunology
Flow Cytometry
Health aspects
Humans
Immune response
Immunity
Immunology
Immunophenotyping
Interferon-gamma - immunology
Interferon-gamma - metabolism
Interleukin-10 - immunology
Interleukin-10 - metabolism
Interleukin-4 - immunology
Interleukin-4 - metabolism
Interleukins
Life Sciences
Mice, Congenic
Mice, Inbred BALB C
Mice, Inbred DBA
Mice, Transgenic
Ovalbumin - immunology
Peptide Fragments - immunology
Physiological aspects
T cells
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
T-Lymphocytes, Regulatory - transplantation
Treatment Outcome
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Summary: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. 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. Col-Treg clones are characterized by their specific cytokine profile (IL-10(high)IL-4(neg)IFN-γ(int)) 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. 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.
ISSN:1478-6354
1478-6362
DOI:10.1186/ar4567