title: Anti-CD137 mAb treatment inhibits experimental autoimmune uveitis by limiting expansion and increasing apoptotic death of uveitogenic T cells.
abstract: OBJECTIVE
  To explore the role of CD137 in the pathogenesis of experimental autoimmune uveitis (EAU) and to compare the inhibitory mechanism of anti-CD137 mAb with other costimulatory blockers.
  
  
  METHODS
  EAU was induced in B10RIII mice, either by immunization with a uveitogenic peptide, IRBP161-180, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of IRBP161-180-specific T cells. The effect of an agonistic anti-CD137 mAb (2A) on the in vivo induction of disease was studied. Subsequently, the mechanism by which anti-CD137 mAb inhibits uveitogenic T-cell activation was investigated, by using the adoptive transfer of T cells derived from anti-CD137 mAb-treated mice, and in vitro, using the proliferative response and apoptotic cell death of IRBP-specific T cells from anti-CD137 mAb-treated mice.
  
  
  RESULTS
  Administration of anti-CD137 mAb prevented the development of de novo induced uveitis, but not that induced by adoptive transfer of pathogenic T cells. Furthermore, anti-CD137 mAb treatment of the animals resulted in decreased expansion of uveitogenic T cells, accompanied by increased activated cell death and resistance to reinduction of uveitis.
  
  
  CONCLUSIONS
  CD137 plays a critical role in the induction, rather than the effector, phase of the disease. Different costimulatory molecules have different effects on the activation of autoreactive T cells by acting in different phases of T-cell activation.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Fu
authors.forename: Tianjiang
authors.initials: T
authors.lastname: Liao
authors.forename: Young
authors.initials: Y
authors.lastname: Peng
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D015866:Uveitis, Posterior / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005136:Eye Proteins; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D012177:Retinol-Binding Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000099214:Retinol-Binding Proteins, Interstitial; C505715:Tnfrsf9 protein, mouse