title: Blockade of the OX40 ligand prolongs corneal allograft survival.
abstract: Although corneal transplantation is one of the most common tissue transplantations and is known to have a high graft acceptance rate, occasional corneal graft rejection remains a cause of blindness. OX40, a member of the TNF receptor superfamily, is expressed on activated T cells, and transmits a costimulatory signal by binding to OX40 ligand (OX40L) expressed on several cells with antigen-presenting functions. Using a blocking monoclonal antibody (mAb) against murine OX40L, we investigated the role of OX40 in a murine model of corneal transplantation. C3H/He mouse corneas were transplanted to BALB/c mice orthotopically. Administration of anti-OX40L mAb significantly reduced allograft rejection, and increased graft survival rate to 40% at 8 weeks after transplantation, while all corneas were rejected within 5 weeks in control IgG-treated mice. Similar reduced rejection was observed when wild-type donor corneas were transplanted to OX40L-deficient recipients. In vitro study revealed that the anti-OX40L mAb treatment reduced proliferative response and IFN-gamma production of draining lymph node cells in response to stimulation with donor alloantigen. These results demonstrate that OX40L blockade is effective for prolongation of corneal allograft survival by inhibiting recipient T cell activation.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Usui
authors.forename: Eiko
authors.initials: E
authors.lastname: Takada
authors.forename: Junichiro
authors.initials: J
authors.lastname: Mizuguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D016039:Corneal Transplantation; D004353:Drug Evaluation, Preclinical; D005136:Eye Proteins / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D053278:OX40 Ligand; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D005136:Eye Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D016753:Interleukin-10; D007371:Interferon-gamma