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Tomoyuki Kunishige, Hiroko Taniguchi, Misao Terada, Hisaya Akiba, Hideo Yagita, Ryo Abe, Junko Hori; Protective Role of ICOS and ICOS Ligand in Corneal Transplantation and in Maintenance of Immune Privilege. Invest. Ophthalmol. Vis. Sci. 2016;57(15):6815-6823. doi: https://doi.org/10.1167/iovs.16-20644.
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© ARVO (1962-2015); The Authors (2016-present)
The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts.
Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS−/− BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed. A separate set of WT and ICOS−/− BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allospecific anterior chamber–associated immune deviation (ACAID) was assessed. In vitro, cornea was incubated with T cells from WT and ICOS−/− BALB/c mice, and destruction of corneal endothelial cells (CECs) and the population of Foxp3+ CD25+ CD4+ T cells was assessed.
Inducible costimulatory molecule ligand mRNA was constitutively expressed in the cornea, iris-ciliary body, and retina. Allograft survival in ICOS−/− recipients and WT recipients treated with anti-ICOSL mAb was significantly shorter than in control recipients. Anterior chamber–associated immune deviation was induced less efficiently in ICOS−/− mice. Destruction of CECs by alloreactive ICOS−/− T cells was enhanced compared with WT T cells. After coincubation with allogeneic corneal tissue, the proportion of regulatory T cells was significantly greater among WT T cells than in ICOS−/− T cells.
The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.
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