Blockade of the OX40 ligand prolongs corneal allograft survival
| Autor: | Hisaya Akiba, Yasushi Sonoda, Junichiro Mizuguchi, Masaru Takeuchi, Hideo Yagita, Yoko Okunuki, Eiko Takada, Takaaki Hattori, Masahiko Usui, Yoshihiko Usui, Ko Okumura |
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| Rok vydání: | 2007 |
| Předmět: |
Graft Rejection
Isoantigens medicine.drug_class T cell medicine.medical_treatment Immunology Drug Evaluation Preclinical OX40 Ligand T-Cell Antigen Receptor Specificity Biology Monoclonal antibody Corneal Transplantation Interferon-gamma Mice Cornea medicine Animals Transplantation Homologous Immunology and Allergy Eye Proteins Lymph node Corneal transplantation Mice Knockout Mice Inbred BALB C Mice Inbred C3H Membrane Glycoproteins Graft Survival Antibodies Monoclonal Tissue Donors Interleukin-10 Blockade Transplantation surgical procedures operative medicine.anatomical_structure Tumor Necrosis Factors Cancer research biology.protein Tumor Necrosis Factor Inhibitors Antibody T-Lymphocytes Cytotoxic |
| Zdroj: | European Journal of Immunology. 37:3597-3604 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200636975 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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