ArticleThe Journal of clinical investigation2012
Viral acute lower respiratory infections impair CD8+ T cells through PD-1.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
131 citing papers in PubMed, 206 citations in OpenAlex.
- Review
- Regulation of antiviral immunity by PD-1 during respiratory syncitial virus infection and upon vaccination.iScience · 2026Article
- Early-life viral infection generates pathological tissue-resident memory cells that contribute to asthma-like disease.JCI insight · 2026Article
- Mechanistic insights and emerging applications of human metapneumovirus (HMPV) treatment: From molecular design to translational immunity.Folia microbiologica · 2026Review
- PD-L1 is an intrinsic switch for natural killer cell-mediated, TRAIL-dependent antiviral function.Cell reports · 2026Article
- TLR7-mediated inflammation drives PD-L1 upregulation and T cell exhaustion during influenza A virus infection.iScience · 2026Article
- Respiratory virus immune response in the aged host.Immunity & ageing : I & A · 2026Review
- Glycans on non-structural protein 1 prevent premature T-cell mediated dengue virus clearance.EMBO molecular medicine · 2025Article
- Human metapneumovirus: understanding the molecular mechanisms and pathology of infection.Journal of virology · 2025Review
- Limited nasal IFN production contributes to delayed respiratory virus clearance and suboptimal vaccine responses.JCI insight · 2025Article
- Activation of PD-1/PD-L1 immune checkpoint by Zika virus.PLoS pathogens · 2025Article
- Th1 differentiation and function are inhibited in neonates following human metapneumovirus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The PD-1/PD-L1 pathway and Epstein-Barr virus.European journal of medical research · 2025Review
- Immunological insights into the re-emergence of human metapneumovirus.Current opinion in immunology · 2025Review
- Positive Regulation of Cellular Proteins by Influenza Virus for Productive Infection.International journal of molecular sciences · 2025Review
- Co-delivery of axitinib and PD-L1 siRNA for the synergism of vascular normalization and immune checkpoint inhibition to boost anticancer immunity.Journal of nanobiotechnology · 2025Article
- Review
- Method to Assess Immunosenescent CD8Methods in molecular biology (Clifton, N.J.) · 2025Article
- Alarm Functions of PD-1+ Brain-Resident Memory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.