Purchase this article with an account.
J. Hori, H. Taniguchi, M. Azuma, H. Akiba, H. Yagita, R. Abe; Role of ICOS/B7RP-1 Pathway in Immune Privilege of Corneal Allografts. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3438.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Interaction between the inducible costimulatory molecule (ICOS) and its ligand, B7-related protein (B7RP)-1, has been reported to have an impact on differentiation and functions of various T regulatory cells. We have previously shown that blockade of B7RP-1 led to a decreased proportion of Foxp3+ICOS+CD4+T cells, and accelerated corneal allograft rejection. To further investigate the mechanisms of ocular immune privilege associated with the ICOS/B7RP-1 pathway, we used ICOS-/- mice for the experimental models of anterior chamber-associated immune deviation (ACAID) and corneal allografts.
Normal corneas of C57BL/6 mice were orthotopically transplanted into normal eyes of W/T and ICOS-/- BALB/c mice, and graft survival was assessed. In a separate experiment, W/T and ICOS-/- BALB/c mice received an 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. W/T recipients received anti-B7RP-1 monoclonal antibody or control IgG intraperitoneally for 3 weeks. Expressions of ICOS and B7RP-1 in ocular tissue were assessed by RT-PCR.
B7RP-1, but not ICOS was expressed in cornea, iris-ciliary body and retina. Allograft survival in the W/T recipients treated with anti-B7RP-1 mAb and in the ICOS-/- mice was significantly shorter than that in the control recipients. Allo-specific ACAID was induced in both W/T mice treated with anti-B7RP-1 mAb and ICOS-/- mice, but the ICOS-/- mice showed a lower suppressive effect than the control mice.
ICOS/B7RP-1 signaling has an immune suppressive effect in corneal allografts, but not much affect on ACAID induction. B7RP-1 expressed on ocular tissue and ICOS expressed on T-cells may interact in the eye and play a role in the survival of the corneal allograft.
This PDF is available to Subscribers Only