April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Role of ICOS/B7RP-1 Pathway in Immune Privilege of Corneal Allografts
Author Affiliations & Notes
  • J. Hori
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • H. Taniguchi
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • M. Azuma
    Molecular Immunology, Tokyo Medical and Dental University, Bunkyo-Ku, Japan
  • H. Akiba
    Immunology, Juntendo University School of Medicine, Bunkyo-Ku, Japan
  • H. Yagita
    Immunology, Juntendo University School of Medicine, Bunkyo-Ku, Japan
  • R. Abe
    Immunology, Research Institute for Biological Science, Tokyo University of Science, Noda, Japan
  • Footnotes
    Commercial Relationships  J. Hori, None; H. Taniguchi, None; M. Azuma, None; H. Akiba, None; H. Yagita, None; R. Abe, None.
  • Footnotes
    Support  This study was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science to J.H.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3438. doi:
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      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: immune tolerance/privilege • ACAID • transplantation 

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