title: The role of costimulatory molecules B7-1 and B7-2 in mice with experimental autoimmune uveoretinitis.
abstract: BACKGROUND
  Onset of experimental autoimmune uveoretinitis (EAU) is believed to involve a CD4-positive type 1 T helper cell (Th1) immune response, with inhibition involving a Th2 immune response. Development of Th1 and Th2 responses involves the participation of the costimulatory molecules B7-1 and B7-2, respectively. The purpose of this study was to investigate the role of B7-1 and B7-2 in the EAU model in mice.
  
  
  METHODS
  B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and given daily intraperitoneal injections of either phosphate-buffered saline (control), mouse monoclonal antibody (mAb) to B7-1, mAb to B7-2, or mAb to both B7-1 and B7-2. Eyes were evaluated by histopathological criteria and cytokines were assayed in culture medium of IRBP-stimulated lymphocytes. Cellular immune responses were measured by cell proliferation assay under IRBP stimulation.
  
  
  RESULTS
  Rates of EAU onset were 5/10 (50%) for control mice, 1/9 (11%) for mice treated with anti-B7-1 mAb, 5/6 (83%) for mice treated with anti-B7-2 mAb, and 2/6 (33%) for mice treated with both anti-B7-1 and anti-B7-2 mAb. Mean histopathological severity scores were 2. 4+/-0.8, 1.0+/-0, 2.6+/-1.0, and 1.0+/-0, respectively. Production of IL-5 was significantly increased in mice treated with anti-B7-1 mAb, while IFN-gamma was increased in mice treated with anti-B7-2 mAb. Spleen cell proliferation was significantly reduced in mice treated with anti-B7-1 mAb.
  
  
  CONCLUSIONS
  These results suggest that the costimulatory molecules B7-1 and B7-2, via their influence on generating Th1 and Th2 immune responses, play an important role in the clinical outcome of EAU in mice immunized with IRBP.
authors.affiliation: Department of Ophthalmology, Tokyo Medical College Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukai
authors.forename: A A
authors.initials: AA
authors.lastname: Okada
authors.forename: J
authors.initials: J
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Kezuka
authors.forename: H
authors.initials: H
authors.lastname: Keino
authors.forename: M
authors.initials: M
authors.lastname: Usui
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: J
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000502:physiology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000633:toxicity; D005260:Female; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012177:Retinol-Binding Proteins / Q000633:toxicity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C497965:Cd86 protein, mouse