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H. Taniguchi, IV, J. Hori, M. C. Wang, Y. Kitahara, H. Takahashi, M. Oshima, H. Yagita; B7-H3 Is Necessary for Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2007;48(13):191.
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We have previously reported that B7-H1 (PD-L1), a new member of the B7 family is constitutively expressed on corneal endothelium and maintains ocular immunosuppressive microenvironments to promote survival of corneal allografts. B7-H3 has been recently identified as another new member of the B7 family, but its expression and function in the eye remain largely unknown. To determine the role of B7-H3 in ocular immune privilege, we used in vivo experimental models including anterior chamber-associated immune deviation (ACAID) and acceptance of corneal allografts.
Normal corneas of C57BL/6 were transplanted orthotopically into normal eyes of BALB/c mice, and graft survival was assessed clinically. In a separate experiment, BALB/c mice received anterior chamber injection of C57BL/6 splenocytes 2 weeks prior to subcutaneous immunization. Induction of allo-specific ACAID was assessed by ear challenge with C57BL/6 splenocytes at 1 week after immunization. Recipients were administrated intraperitoneally with 0.2 mg of anti-B7-H3 monoclonal antibody or control rat IgG, three times a week for 8 weeks after corneal grafting, and for 3 weeks after AC injection. Expression of B7-H3 in normal and in graft-bearing eyes was assessed immunohistochemically by confocal microscopy.
B7-H3 was expressed on the corneal endothelium and iris-ciliary body of both normal corneas and allografts. Treatment with anti-B7-H3 monoclonal antibody abolished allo-specific ACAID induction. Allograft-survival in the recipients treated with anti-B7-H3 monoclonal antibody were significantly less than that in the control recipients at 8 weeks.
B7-H3 is constitutively expressed on corneal endothelium and iris-ciliary body. B7-H3 plays important role in the maintenance of ocular immune privilege, such as ACAID and acceptance of corneal allografts.
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