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

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Asnagli H, Martire D, Belmonte N, Quentin J, Bastian H, Boucard-Jourdin M, Fall PB, Mausset-Bonnefont AL, Mantello-Moreau A, Rouquier S, Marchetti I, Jorgensen C, Foussat A, Louis-Plence P

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

Arthritis Res Ther. 2014 May 22;16(3):R115. doi: 10.1186/ar4567.

PubMed ID
24886976 [ View in PubMed
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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-10(high)IL-4(neg)IFN-gamma(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. 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.

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