title: Galectin-9-mediated protection from allo-specific T cells as a mechanism of immune privilege of corneal allografts.
abstract: The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan. machiko@jichi.ac.jp
authors.forename: Machiko
authors.initials: M
authors.lastname: Shimmura-Tomita
authors.forename: Mingcong
authors.initials: M
authors.lastname: Wang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Junko
authors.initials: J
authors.lastname: Hori
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D016039:Corneal Transplantation; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004728:Endothelium, Corneal / Q000473:pathology; D037161:Galectins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D007109:Immunity / Q000276:immunology*; D008221:Lymphoid Tissue / Q000378:metabolism; D008297:Male; D051379:Mice; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C508186:galectin 9, mouse