title: Inhibition of Noninfectious Uveitis Using Intravenous Administration of Collagen II-Specific Type 1 Regulatory T Cells.
abstract: OBJECTIVE
  To evaluate the therapeutic potential of Col-Treg, a collagen II-specific type 1 regulatory T-cell immunotherapy for the treatment of noninfectious uveitis (NIU).
  
  
  METHODS
  Col-Treg cells were produced from collagen II-specific T cell receptor (TCR) transgenic mice or peripheral blood of healthy donors. Phenotypic characterization was performed by flow cytometry, and cytokine secretion was evaluated with Flowcytomix or ELISA. In vitro functional characterization included ATP hydrolysis, cytotoxicity, and contact-independent T-cell suppression and plasticity assays. Col-Treg migration was assessed by quantitative PCR specific to Col-Treg TCR. Col-Treg cells were administered intravenously in mice displaying experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) immunizations. Efficacy of Col-Treg was assessed by ophthalmology, histology, and immunohistochemistry.
  
  
  RESULTS
  Mice Col-Treg cells displayed identity features of type 1 Treg cells with expression of CD25, FoxP3, low surface expression of CD127, and cytokine secretion profile (IL-10(high), IL-4(low), IFN-γ(int)). In vitro functional assays demonstrated Col-Treg suppressive capacity via soluble factor-dependent immunosuppression, cytotoxicity, and ATP hydrolysis. Col-Treg cells expressed granzyme B, CD39, and glucocorticoid-induced TNF-related protein (GITR). Administration of Col-Treg in EAU mice inhibited clinical and morphologic signs of uveitis and decreased ocular leukocyte infiltration. Col-Treg cells homed in the ocular tissues 24 hours after intravenous injection. Human Col-Treg cells were comparable to mice Col-Treg cells in identity and function and did not show the capacity to differentiate into Th17 cells in vitro.
  
  
  CONCLUSIONS
  These results demonstrate the therapeutic potential of Col-Treg cells as a targeted approach for the treatment of NIU and the feasibility of translating this approach to the human clinical setting.
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Asnagli
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Jacquin
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Belmonte
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gertner-Dardenne
authors.affiliation: COLA, Jozerand, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Hubert
authors.affiliation: VETOPATH, Antibes, France.
authors.forename: André
authors.initials: A
authors.lastname: Sales
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Papa Babacar
authors.initials: PB
authors.lastname: Fall
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Ginet
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Irène
authors.initials: I
authors.lastname: Marchetti
authors.affiliation: VETOPATH, Antibes, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Ménard
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Lara
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bobak
authors.affiliation: TxCell Valbonne Sophia-Antipolis, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Foussat
mesh_terms: D000818:Animals; D024043:Collagen Type II / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D007275:Injections, Intravenous; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D024043:Collagen Type II