Human Corneal Endothelial Cells Expressing Programmed Death-Ligand 1 (PD-L1) Suppress PD-1+T Helper 1 Cells by a Contact-Dependent Mechanism

Citations Over TimeTop 13% of 2009 papers

Abstract

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.

Related Papers

• → Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine(2020)18 cited
• Evidence of in vitro development of drug resistance to azidothymidine in T-lymphocytic leukemia cell lines (Jurkat E6-1/AZT-100) and in pediatric patients with HIV-1 infection.(1993)
• → [Oridonin inhibits proliferation of Jurkat cells via the down-regulation of Brg1].(2017)1 cited
• [MEKK2 regulates the production of interleukin 2].(2005)
• Effect of Programmed Death Ligand-1 signal on activity and apoptosis of Jurkat cell.(2010)