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

• DOI: 10.1186/ar4567
• Publication Date: 2014-05-22T09:07:35Z
• Authors: Hélène Asnagli; Delphine Martire; Nathalie Belmonte; Julie Quentin; Hervé Bastian; Mathilde Boucard-...; Papa Babacar Fall; Anne-Laure Mausse...; Amélie Mantello-M...; Sandrine Rouquier; Irène Marchetti; Christian Jorgensen; Arnaud Foussat; Pascale Louis-Plence
• Keywords: 0301 basic medicine; Ovalbumin; Immunology; Mice, Transgenic; T-Lymphocytes, Regulatory; Immunophenotyping; Arthritis, Rheumatoid; Interferon-gamma; Mice, Congenic; 03 medical and health sciences; Rheumatology; Immunology and Allergy; Animals; Humans; Collagen Type II; Cells, Cultured; Cell Proliferation; Mice, Inbred BALB C; Flow Cytometry; Adoptive Transfer; Arthritis, Experimental; Peptide Fragments; Interleukin-10; 3. Good health; Mice, Inbred DBA; [SDV.IMM]Life Sciences [q-bio]/Immunology; Interleukin-4; Research Article

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.