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J. Hori, H. Taniguchi, M. Wang, H. Akiba, H. Yagita; Protective Role of ICOS/B7RP-1 Pathway in Acceptance of Corneal Allografts. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3035.
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The inducible costimulatory molecule (ICOS) is a member of the CD28/CTLA-4 family. Interaction between ICOS and its ligand, B7 related protein (B7RP)-1, has been reported to promote T cell responses. It has also been indicated that ICOS has an impact on differentiation and functions of various T regulatory cells, such as naturally occurring T regulatory cells, Tr1, and CD8+ T regulatory cells. The purpose of the present study is to investigate the role of ICOS/B7RP-1 pathway in immune responses after corneal allo-transplantation.
Normal corneas of C57BL/6 were transplanted orthotopically into normal eyes of BALB/c mice. Recipients were administrated intraperitoneally with 0.25 mg of anti-B7RP-1 monoclonal antibody (mAb) or isotype control rat IgG three times a week for 3 weeks after grafting. Graft survival and corneal neovascurlarization were evaluated. Acquisition of donor-specific delayed type hypersensitivity in the recipients was assessed. C57BL/6 cornea was also transplanted in the eyes of BALB/c mice depleted CD25+CD4+ T regulatory cells by the previous administration of a high dose of anti-CD25 mAb. ICOS expression in the cervical lymph nodes in the allograft-bearing recipients was assessed by flowcytometry.
Allograft survival in the recipients treated with anti-B7RP-1 mAb was significantly shorter than that in the control recipients. Donor-specific delayed hypersensitivity was induced in the recipients with ICOS/B7RP-1 blockade. Neovascularization into the corneal allografts in the recipients treated with anti-B7RP-1 mAb was significantly more sever than that in the control recipients. In the cervical lymph nodes of the CD25+CD4+Treg-depleted recipients bearing corneal allografts, the proportion of ICOS+CD8+T cells increased.
ICOS/B7RP-1 pathway plays a protective role in acceptance of corneal allografts. ICOS/B7RP-1 signaling may be mutually influenced by T regulatory cells in immune responses after corneal allo-transplantation.
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