Blockade of the OX40 ligand prolongs corneal allograft survival

• Published in: European journal of immunology 2007-12, Vol.37 (12), p.3597-3604
• Main Authors: Hattori, Takaaki, Usui, Yoshihiko, Okunuki, Yoko, Sonoda, Yasushi, Usui, Masahiko, Takada, Eiko, Mizuguchi, Junichiro, Yagita, Hideo, Okumura, Ko, Akiba, Hisaya, Takeuchi, Masaru
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Cornea; Corneal Transplantation; Costimulatory molecule; Drug Evaluation, Preclinical; Eye Proteins - immunology; Graft Rejection - prevention & control; Graft Survival - drug effects; Immune modulation; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Isoantigens - immunology; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Knockout; T-Cell Antigen Receptor Specificity; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Tissue Donors; Transplantation; Transplantation, Homologous; Tumor Necrosis Factors - antagonists & inhibitors; Tumor Necrosis Factors - deficiency; Tumor Necrosis Factors - genetics; Tumor Necrosis Factors - physiology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200636975

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-γ 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.