May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Role of Glucocorticoid-Induced TNF Receptor Ligand in Immune Privilege of Corneal Allografts
Author Affiliations & Notes
  • J. Hori
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • M. C. Wang
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • H. Taniguchi
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • Y. Kitahara
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • H. Takahashi
    Ophthalmology, Nippon Medical School, Bunkyo-Ku, Japan
  • M. Oshima
    Immunology, National Institute of Infectious Disease, Tokyo, Japan
  • S. Sakaguchi
    Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
  • M. Azuma
    Molecular Immunology, Tokyo Medical and Dental University, Tokyo, Japan
  • Footnotes
    Commercial Relationships J. Hori, None; M.C. Wang, None; H. Taniguchi, None; Y. Kitahara, None; H. Takahashi, None; M. Oshima, None; S. Sakaguchi, None; M. Azuma, None.
  • Footnotes
    Support Grant-in-Aid for Scientific Research(C) from the Japan Society for the Promotion of Science
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3627. doi:
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      J. Hori, M. C. Wang, H. Taniguchi, Y. Kitahara, H. Takahashi, M. Oshima, S. Sakaguchi, M. Azuma; Role of Glucocorticoid-Induced TNF Receptor Ligand in Immune Privilege of Corneal Allografts. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3627.

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

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Purpose:: The pathway between glucocorticoid-induced TNF receptor family-related protein (GITR) and its ligand (GITRL) has been shown to control the function of regulatory T cells (Treg). To investigate the role of this pathway in ocular immune privilege, we used in vivo experimental models including anterior chamber-associated immune deviation (ACAID) and acceptance of corneal allografts.

Methods:: Normal corneas of C57BL/6 mice were orthotopically transplanted into normal eyes of BALB/c mice, and graft survival was assessed. 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 intraperitoneally administrated agonistic anti-GITR (DTA-1) or antagonistic anti-GITRL (MIH44) monoclonal antibodies (mAb), or control IgG, for 8 weeks after corneal grafting, and for 3 weeks after AC injection. Expressions of GITRL, GITR, and Treg-specific transcription factor Foxp3 in normal and graft-bearing eyes were assessed immunohistochemically by confocal microscopy.

Results:: GITRL was expressed constitutively in the corneal endothelium, iris-ciliary body and retinal pigment epithelium. Treatment with DTA-1 or MIH44 did not affect allo-specific ACAID, but led to accelerated corneal allograft rejection. GITRL-expressing corneal allografts were infiltrated with Foxp3(+)GITR(+)CD4(+)T-cells, during which allograft acceptance occurred. In contrast, blockade of GITRL led to infiltration of a number of Foxp3(-)GITR(+)CD4(+)T-cells into allografts, leading to allograft rejection.

Conclusions:: T-cell stimulation through GITR by agonistic mAb enhances effector T-cell responses against corneal allografts. On the contrary, GITRL expressed on corneal endothelium plays a role in the acceptance of corneal allografts, via Treg-mediated suppression within the cornea.

Keywords: immune tolerance/privilege • transplantation • ACAID 

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