Abstract
Introduction: Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an idealtarget 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), whichcontributes to their ability to suppress pathological immune responses in several settings. The aim of this study wasto evaluate the therapeutic potential of collagen type II–specific Tr1 (Col-Treg) cells in two models of rheumatoidarthritis (RA) in mice.Methods: Col-Treg clones were isolated and expanded from collagen-specific TCR transgenic mice. Their cytokinesecretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells wasevaluated after adoptive transfer in collagen-antibody– and collagen-induced arthritis models. The in vivosuppressive 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 mediatecontact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 andgranzyme B. A single infusion of Col-Treg cells reduced the incidence and clinical symptoms of arthritis in bothpreventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection ofantigen-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, providingevidence that Col-Treg could be an efficient cell-based therapy for RA patients whose disease is refractory to currenttreatments.