RGD Reference Report - Viral acute lower respiratory infections impair CD8+ T cells through PD-1. - Rat Genome Database

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Viral acute lower respiratory infections impair CD8+ T cells through PD-1.

Authors: Erickson, John J  Gilchuk, Pavlo  Hastings, Andrew K  Tollefson, Sharon J  Johnson, Monika  Downing, Melissa B  Boyd, Kelli L  Johnson, Joyce E  Kim, Annette S  Joyce, Sebastian  Williams, John V 
Citation: Erickson JJ, etal., J Clin Invest. 2012 Aug;122(8):2967-82. doi: 10.1172/JCI62860. Epub 2012 Jul 17.
RGD ID: 40818270
Pubmed: (View Article at PubMed) PMID:22797302
DOI: Full-text: DOI:10.1172/JCI62860

Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8+ cytotoxic T lymphocyte (TCD8) functional impairment via programmed death-1/programmed death ligand-1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1-mediated TCD8 impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory TCD8 rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented TCD8 impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates TCD8 functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses.

Disease Annotations    
Viral Bronchiolitis  (IEP,IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Cd274  (CD274 molecule)
Pdcd1  (programmed cell death 1)

Genes (Mus musculus)
Cd274  (CD274 antigen)
Pdcd1  (programmed cell death 1)

Genes (Homo sapiens)
CD274  (CD274 molecule)
PDCD1  (programmed cell death 1)

Additional Information