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H. Taniguchi, M. C. Wang, Y. Kitahara, M. Oshima, H. Yagita, J. Hori; B7-H3-Mediated Protection of Corneal Endothelial Cells From Killing by Allo-Reactive-T Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):437. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
B7-H3 is a new member of the B7 family of costimulatory molecules for antigen recognition. We have demonstrated that B7-H3 is constitutively expressed on corneal endothelium and the iris-ciliary body and plays important roles in the maintenance of ocular immune privilege, such as anterior chamber-associated immune deviation (ACAID) and acceptance of corneal allografts. To further investigate the mechanisms B7-H3-associated immune suppression, we examined destruction of corneal endothelial cells (CECs) by allo-reactive T cells in vitro. We also analyzed expression of B7-H3 in secondary lymphoid organs after corneal allografting.
Corneas from C57BL/6 (B6) eyes pre-treated with anti-B7-H3 mAb or control rat IgG were incubated with CD4+ T cells for 6 h. CD4+ T cells were purified from the spleen of BALB/c mice that were presensitized by subcutaneous immunization with B6 splenocytes or with third-party (C3H/He) splenocytes, or from the spleen of naive BALB/c, B6 or C3H/He mice. Dead CECs stained with propidium iodide were counted and compared. As a different set of experiments, spleens and lymph nodes (LNs) of recipients bearing accepted or rejected allografts were harvested, and expression of B7-H3 on splenocytes and LN cells was analyzed by flow cytometry. Normal BALB/c mice and recipients bearing syngeneic corneal grafts were used as controls.
The number of dead CECs in anti-B7-H3 mAb-treated corneas were significantly larger than that in control IgG-treated corneas after incubation with allo-reactive T cells. Interestingly, the number of dead CECs in anti-B7-H3 mAb-treated corneas was significantly larger than that in control IgG-treated corneas after incubation with activated T cells against third-party allo-antigens. In contrast, no significant differences were observed between anti-B7-H3 mAb and control IgG-treated corneas with naive BALB/c or C3H/He T cells. Very few B7-H3-expressing cells were seen in the spleen and LNs in both recipients of corneal grafts and normal mice.
B7-H3 expressed on CECs plays a role in protecting CECs from destruction by activated CD4+ T cells. Since B7-H3 is rarely expressed in the spleen and LN after corneal allografting, B7-H3-mediated immune suppression involves local effects within the cornea, rather than in secondary lymphoid organs.
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