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Misao Terada, Hiroko Taniguchi, Ryo Abe, Junko Hori; Inhibitory Role of ICOS in Antigen-specific T cell-mediated Ocular Tissue Damage. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6187.
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Inducible costimulatory molecule (ICOS) is a costimulatory molecule that interacts with B7RP-1 to regulate T cell function. Locally expressed in the eye, B7RP-1 plays an immunosuppressive role via ICOS expressed in infiltrating cells, and we have previously reported its importance in allograft survival. The present study analyzed the role of ICOS in interactions between ocular tissue and T cells.
Wild-type BALB/c mice and ICOS-knockout BALB/c mice were immunized with either C57BL/6 (allo) or C3H/HE (third party) splenocytes. Splenic T cells purified from these wild-type (WT-T cells) and ICOS-knockout mice (ICOS-KO-T cells), were cocultured with C57BL/6 corneal tissue. Dead corneal endothelial cells (CECs) were then quantitatively analyzed under confocal microscopy with propidium iodide staining. Flow cytometry was used to analyze the proportion of Foxp3+CD4+CD25+T cells (Treg) pre- and post-coculture.
In post-coculture of corneal tissue and T cells, CEC damage due to alloreactive T cells was significantly greater in ICOS-KO-T cells than in WT-T. In both ICOS-KO-T cells and WT-T cells cultured without corneal tissue, the proportion of Treg remained unchanged. However, after coculture with corneal tissue, the proportion of Treg in WT-T cells increased significantly. This increase was also significantly greater than that observed in ICOS-KO-T cells.
In the interaction between T cells and corneal tissue, a Treg increase occurs dependent on ICOS expression on the T cell surface. This suggests that the local expansion of ICOS-expressing Treg suppresses corneal damage caused by alloreactive T cells.
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