PD–1 and PD ligand are necessary for corneal allograft survival

Abstract

Abstract: : Purpose: Programmed death 1 (PD–1) is a new member of the CD28/CTLA–4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD–1, namely B7–H1 (PD–L1) and B7–DC (PD–L2), have been identified as new members of the B7 family but their expression and function in the eye remain largely unknown. The purpose of the present study was to determine the role of PD–1 and PD ligands in immune privilege of corneal allografts. Methods: Normal corneas of C57BL/6 were transplanted orthotopically into normal eyes of BALB/c mice. Recipients were administrated intraperitoneally with 0.2 mg of anti–PD–1, anti–B7–H1, anti–B7–DC monoclonal antibodies, or control rat IgG, three times a week for 8 weeks after grafting. Graft survival was assessed clinically and was compared. Expression of PD–1, B7–H1, and B7–DC in normal corneas and in allografts was assessed immunohistochemically by confocal microscopy. Results: Allografts survival in anti–PD–1 group ( 0 % ) and that in anti–B7–H1 group ( 0 % ) were significantly less than that in the control group ( 50 % ) at 8 weeks. Differences between allografts survival in anti–B7–DC group and that in control group were statistically indistinguishable. B7–H1 was expressed on the corneal endothelium of both normal corneas and allografts. PD–1 expression was found on inflammatory cells in the posterior surface of allografts. Conclusions: B7–H1 is constitutively expressed on corneal endothelium. Interaction between B7–H1 and PD–1 plays important role in the maintenance of ocular immune privilege and in high success of corneal allografts transplantation.

Keywords: immune tolerance/privilege • immunomodulation/immunoregulation • transplantation