title: Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis.
abstract: OBJECTIVE
  To investigate whether supplementation of natural CD4+CD25+ regulatory T cells ameliorates mouse experimental autoimmune uveoretinitis (EAU) induced by CD4+ T cell-dependent interphotoreceptor retinoid-binding protein (IRBP).
  
  
  METHODS
  C57BL/6 mice were immunised with human interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP(1-20)), and IRBP(1-20)-sensitised T cells were obtained. CD4+CD25+ T cells derived from naive mice were cocultured with IRBP(1-20)-sensitised T cells, and their proliferation responses and cytokine production were measured. In addition, CD4+CD25+ T cells were transferred intravenously into mice 7 or 15 days after immunisation with IRBP(1-20), and the severity of EAU and T cell proliferation responses were evaluated.
  
  
  RESULTS
  CD4+CD25+ regulatory T cells effectively inhibited both the proliferation of, and interleukin (IL)2, IL5 and interferon (IFN)gamma production by, IRBP(1-20)-sensitised T cells. Adoptive transfer of CD4+CD25+ regulatory T cells to IRBP(1-20)-immunised mice conferred considerable protection from EAU development and inhibition of T cell proliferation responses to IRBP(1-20).
  
  
  CONCLUSIONS
  These findings show that natural CD4+CD25+ regulatory T cells possess the ability to inhibit activation of IRBP-reactive T cells that have been already sensitised in vivo, and adoptive transfer of these cells ameliorates EAU even in the effector phase. Supplementation of natural CD4+CD25+ regulatory T cells may have therapeutic potential for effective treatment of uveitis.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Keino
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Usui
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: N
authors.initials: N
authors.lastname: Yamakawa
authors.forename: T
authors.initials: T
authors.lastname: Kezuka
authors.forename: J-I
authors.initials: JI
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Usui
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012173:Retinitis / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C498833:Foxp3 protein, mouse