title: Ocular inflammation in HLA-B27 transgenic mice reveals a potential role for MHC class I in corneal immune privilege.
abstract: OBJECTIVE
  HLA-B27 is a major histocompatibility complex class I (MHCI) allele that has been closely associated with the development of ankylosing spondylitis and acute anterior uveitis (AAU), the most common form of uveitis worldwide. We have been characterizing the phenotypes of transgenic mice carrying a human HLA-B27 allele, but that are deficient in endogenous mouse MHCI genes (H-2K(-/-) and H-2D(-/-) double knockout, or DKO) to create the HLA-B27/DKO line. In maintaining and expanding this colony, we observed a rare sporadic severe central keratitis that developed in transgenic animals, but that was not present in wild-type (WT) animals.
  
  
  METHODS
  The corneas of affected HLA-B27/DKO and DKO mice were compared to their WT counterparts by staining with standard histological methods for markers of inflammation and neovascularization. A model of experimental corneal inflammation was subsequently used to test the responses of each genotype to insult.
  
  
  RESULTS
  We identified a previously unreported corneal pathology in naïve HLA-B27/DKO mice, and we describe significantly prolonged CD4(+)- and CD8(+)-associated inflammation in these animals following an experimentally induced corneal injury.
  
  
  CONCLUSIONS
  These results demonstrate an increased T-cell response in B27/DKO corneas due to the expression of the HLA-B27 allele, suggesting that low MHCI expression in WT corneas is an important contributor to immune privilege.
authors: Division of Genes and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors: Aifeng
authors: A
authors: Lin
authors: Division of Vision Sciences, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors: Xiaoxin
authors: X
authors: Guo
authors: Division of Genes and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors: Robert D
authors: RD
authors: Inman
authors: Division of Vision Sciences, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada ; Department of Ophthalmology and Vision Science, University of Toronto, Toronto, Ontario, Canada.
authors: Jeremy M
authors: JM
authors: Sivak
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003315:Cornea / Q000276:immunology / Q000473:pathology*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D064532:Histocompatibility Antigen H-2D / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007634:Keratitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019076:Transgenes
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015796:HLA-B27 Antigen; D064532:Histocompatibility Antigen H-2D