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RSV-Induced Bronchial Epithelial Cell PD-L1 Expression Inhibits CD8+ T Cell Nonspecific Antiviral Activity

By Aurica G. Telcian, Vasile Laza-Stanca, Michael R. Edwards, James A. Harker, Hongwei Wang, Nathan W. Bartlett, Patrick Mallia, Mihnea T. Zdrenghea, Tatiana Kebadze, Anthony J. Coyle, Peter J.M. Openshaw, Luminita A. Stanciu and Sebastian L. Johnston

Abstract

Respiratory syncytial virus (RSV) is a major cause of bronchiolitis in infants. It is also responsible for high morbidity and mortality in the elderly. Programmed death ligands (PD-Ls) on antigen-presenting cells interact with receptors on T cells to regulate immune responses. The programmed death receptor-ligand 1/programmed death receptor 1 (PD-L1-PD-1) pathway is inhibitory in chronic viral infections, but its role in acute viral infections is unclear. We hypothesized that bronchial epithelial cell (BEC) expression of PD-Ls would inhibit local effector CD8+ T cell function. We report that RSV infection of primary human BECs strongly induces PD-L1 expression. In a co-culture system of BECs with purified CD8+ T cells, we demonstrated that RSV-infected BECs increased CD8+ T cell activation, proliferation, and antiviral function. Blocking PD-L1 on RSV-infected BECs co-cultured with CD8+ T cells enhanced CD8+ T cell IFN-γ, IL-2, and granzyme B production. It also decreased the virus load of the BECs. Based on our findings, we believe therapeutic strategies that target the PD-L1-PD-1 pathway might increase antiviral immune responses to RSV and other acute virus infections

Topics: Major Articles and Brief Reports
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:3086441
Provided by: PubMed Central
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