title: CCR5-deficient mice develop experimental autoimmune uveoretinitis in the context of a deviant effector response.
abstract: OBJECTIVE
  Experimental autoimmune uveoretinitis (EAU) is an organ-specific, Th1-cell-mediated disease that targets the neural retina. CCR5 is a chemokine receptor expressed on Th1 cells that promotes their migration. In CCR5-deficient mice, we examined the role of CCR5 in the development of EAU induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide.
  
  
  METHODS
  Wild-type or CCR5-deficient B6 mice were immunized with human IRBP peptide 1-20 (hIRBP-p), and the severity of EAU was assessed clinically and histologically. Splenocytes and cells of regional lymph nodes near the eye were collected and their proliferation and production of IL-6, IL-10, IFN-gamma, and CCL2 (MCP-1) in response to hIRBP-p stimulation were measured. Moreover, the intraocular levels of these cytokines were analyzed.
  
  
  RESULTS
  Immunization with hIRBP-p induced EAU in CCR5-deficient mice with a severity comparable to that in wild-type mice. Histologically, T-cell infiltration of the eye was reduced, but granulocyte infiltration was augmented in CCR5-deficient mice. Although splenic T cells from CCR5-deficient mice produced IFN-gamma but not IL-10 on stimulation by hIRBP-p, T cells from the regional lymph nodes failed to produce both cytokines. IL-6 production in the eye and IL-6 and CCL2 production by splenic T cells were predominantly augmented in CCR5-deficient mice.
  
  
  CONCLUSIONS
  The development of EAU is not prevented in CCR5-deficient mice. Although T-cell infiltration into the eye is apparently reduced in CCR5-deficient mice, the defect is compensated for by granulocyte infiltration, supposedly mediated by augmented intraocular production of IL-6.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Haino
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Usui
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000633:toxicity; D005260:Female; D007114:Immunization; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019713:Receptors, CCR5 / Q000502:physiology*; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000633:toxicity; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D019713:Receptors, CCR5; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial