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Hiroko Taniguchi, Tomoyuki Kunishige, Hisaya Akiba, Hideo Yagita, Ryo Abe, Junko Hori; Expression of ICOS and Foxp3 on T cells infiltrating in corneal allografts. Invest. Ophthalmol. Vis. Sci. 2016;57(12):318.
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© 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 ICOS/B7RP-1 led to an accelerated corneal allograft rejection. B7RP-1, but not ICOS, was expressed in the cornea, iris-CB and retina. The mRNA expression level of B7RP-1, but not ICOS, increased in the accepted allografts. On the other hands, the mRNA expression level of ICOS increased and B7RP-1 decreased in the rejected allografts. To further investigate the role of ICOS on regulatory T cell (Treg) in the cornea and its mechanisms after corneal transplantation.
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. Expression of ICOS in normal cornea and expression of ICOS and Foxp3 on CD4+ T cells infiltrating in graft-bearing eyes at 2 to 4 weeks after corneal transplantation was assessed immunohistochemically by confocal microscopy.
There was no expression of ICOS in the normal cornea. ICOS+Foxp3(-)CD4+ T cells were increased in the rejected allografts, and ICOS+Foxp3+CD4+ Treg were present in the accepted allografts at host-graft junction in W/T mice. The number of ICOS+Foxp3+CD4+ Treg was significantly lower than that of ICOS+Foxp3(-)CD4+ T cells at the rejected graft junction in W/T mice (p=0.012). In ICOS-/- mice, Foxp3+CD4+ and Foxp3(-)CD4+ T cells infiltrated at host-graft junction. The number of Foxp3(-)CD4+ T cells in the rejected allograft were increased in comparison with that of the surviving allograft in ICOS-/- mice. Eventually, all the allografts was rejected in ICOS-/- mice.
It is suggested that ICOS+Foxp3+CD4+ Treg infiltrating in corneal allografts has a role in graft acceptance. Foxp3+CD4+ Treg infiltrating into allograft in ICOS-/- mice has insufficient role to promote graft acceptance. Thus, ICOS signal is necessary on immune suppressive function of Foxp3+CD4+ Treg in cornal allo-transplanation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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