期刊
JOURNAL OF INFECTIOUS DISEASES
卷 203, 期 1, 页码 85-94出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiq020
关键词
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资金
- AstraZeneca
- Centocor
- GlaxoSmithKline
- MedImmune
- Sandi-Pasteur
- Synairgen
- British Lung Foundation [P04/13]
- Wellcome Trust [083567/Z/07/Z]
- NIHR Biomedical Research Centre
- UCB Institute of Allergy, European Respiratory Society [33]
- BMA HC [P24259, PO 7269]
- Asthma UK [05/067]
- Medical Research Council [G1000758B, G1000758] Funding Source: researchfish
- National Institute for Health Research [CL-2008-21-014] Funding Source: researchfish
- Asthma UK [S06/001] Funding Source: researchfish
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-gamma, 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.
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