title: Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis.
abstract: BACKGROUND
  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-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.
  
  
  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.
authors.forename: Hélène
authors.initials: H
authors.lastname: Asnagli
authors.forename: Delphine
authors.initials: D
authors.lastname: Martire
authors.forename: Nathalie
authors.initials: N
authors.lastname: Belmonte
authors.forename: Julie
authors.initials: J
authors.lastname: Quentin
authors.forename: Hervé
authors.initials: H
authors.lastname: Bastian
authors.forename: Mathilde
authors.initials: M
authors.lastname: Boucard-Jourdin
authors.forename: Papa Babacar
authors.initials: PB
authors.lastname: Fall
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Mausset-Bonnefont
authors.forename: Amélie
authors.initials: A
authors.lastname: Mantello-Moreau
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rouquier
authors.forename: Irène
authors.initials: I
authors.lastname: Marchetti
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Foussat
authors.forename: Pascale
authors.initials: P
authors.lastname: Louis-Plence
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D024043:Collagen Type II; C111390:OVA 323-339; D010446:Peptide Fragments; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin