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Sunao Sugita, Yoshihiko Usui, Shintaro Horie, Yuri Futagami, Yukiko Yamada, Juan Ma, Takeshi Kezuka, Hirofumi Hamada, Tomohiko Usui, Manabu Mochizuki, Satoru Yamagami; Human Corneal Endothelial Cells Expressing Programmed Death-Ligand 1 (PD-L1) Suppress PD-1+ T Helper 1 Cells by a Contact-Dependent Mechanism. Invest. Ophthalmol. Vis. Sci. 2009;50(1):263-272. doi: 10.1167/iovs.08-2536.
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purpose. This study was designed to determine whether human corneal endothelial (HCE) cells could regulate the activation of bystander T cells in vitro.
methods. HCE cell lines were established from primary HCE cells. Target-activated T cells were used allogeneic T cells and Jurkat T-cell lines. As an additional target, T-cell clones from uveitis patients were established from aqueous humor via a limiting dilution. T-cell activation was assessed for proliferation by [3H]-thymidine incorporation, carboxyfluorescein succinimidyl ester incorporation, or IFNγ production. Expression of co-stimulatory molecules on IFNγ-treated corneal endothelial and non-treated cells was evaluated by flow cytometry, RT-PCR, or immunohistochemistry. Expression of co-stimulatory receptors on target T cells was evaluated by flow cytometry. Blocking antibodies was used to abolish the HCE-inhibitory function.
results. HCE cells suppressed both in vitro proliferation and IFNγ production by CD4+ T cells via a cell contact-dependent mechanism. HCE constitutively expressed co-stimulatory molecules programmed death-ligand 1 (PD-L1) and PD-L2, and their expression was enhanced by IFNγ. HCE efficiently inhibited the proliferation of Th1 cells that overexpressed PD-1 among various activated T-cell lines and clones established from patients with uveitis or corneal endotheliitis. A neutralizing mAb for PD-L1, but not PD-L2, blocked the suppressive effect of HCE on Th1 cells.
conclusions. HCE can impair the effector functions and activation of Th1 infiltrating CD4+ T cells via the PD-1/PD-L1 interaction. The data support the hypothesis that corneal endothelium may contribute to maintenance of the privileged immune status of the anterior chamber of the eye by inducing peripheral immune tolerance.
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