OX40–OX40 Ligand Blockade Facilitate Long Term Corneal Allograft Survival

Abstract

Purpose: : OX40 is the member of TNF receptor superfamily and have costimulatory function. OX40L which is the ligand of OX40 belongs to the TNF family. We investigated the role of OX40 in murine model of corneal transplantation using monoclonal antibody against murine OX40 Ligand and OX40 deficient mice.

Methods: : Expression of OX40 upon rejected mice lymphocytes from draining lymphnodes were studied by FACS analysis. And we investigated the role of OX40 in murine model of corneal transplantation using monoclonal antibody against murine OX40 Ligand. C3H/He mice corneas were transplanted to BALB/c mice orthotopically. Additionally, we performed corneal transplantation using mice genetically knocked out OX40L (OX40 KO) as recipients or donors.

Results: : FACS analysis revealed that OX40 expression was up–regulated in rejected mice lymphocytes. The survival rate of 8 weeks after corneal transplantation was 40% whereas all mice corneas treated with control antibodies were rejected within 5 weeks. Additionally, we performed corneal transplantation using mice genetically knocked out OX40L (OX40 KO) as recipients. As same as administration of anti–OX40 antibody, OX40 KO mice prolonged allograft survival. But when corneal transplantation using OX40 KO mice as donors was performed, all corneas were rejected promptly.

Conclusions: : These results suggest that OX40–OX40L interaction have an important role in corneal transplant rejection, and blockade of OX40–OX40L interaction prolonged corneal graft survival.

Keywords: transplantation • cornea: basic science • cell-cell communication