title: Protective Role of ICOS and ICOS Ligand in Corneal Transplantation and in Maintenance of Immune Privilege.
abstract: The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts.
  
  
  
  Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS-/- BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed. A separate set of WT and ICOS-/- BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. In vitro, cornea was incubated with T cells from WT and ICOS-/- BALB/c mice, and destruction of corneal endothelial cells (CECs) and the population of Foxp3+ CD25+ CD4+ T cells was assessed.
  
  
  
  Inducible costimulatory molecule ligand mRNA was constitutively expressed in the cornea, iris-ciliary body, and retina. Allograft survival in ICOS-/- recipients and WT recipients treated with anti-ICOSL mAb was significantly shorter than in control recipients. Anterior chamber-associated immune deviation was induced less efficiently in ICOS-/- mice. Destruction of CECs by alloreactive ICOS-/- T cells was enhanced compared with WT T cells. After coincubation with allogeneic corneal tissue, the proportion of regulatory T cells was significantly greater among WT T cells than in ICOS-/- T cells.
  
  
  
  The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kunishige
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Laboratory Animal Research Center, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Terada
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Research Institute for Biological Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hori
mesh_terms: D000818:Animals; D003315:Cornea / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016039:Corneal Transplantation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007111:Immunity, Cellular; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000096:biosynthesis / Q000235:genetics*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D012333:RNA, Messenger