ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Programmed death-1 impairs secondary effector lung CD8⁺ T cells during respiratory virus reinfection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Review
- Regulation of antiviral immunity by PD-1 during respiratory syncitial virus infection and upon vaccination.iScience · 2026Article
- Mechanistic insights and emerging applications of human metapneumovirus (HMPV) treatment: From molecular design to translational immunity.Folia microbiologica · 2026Review
- Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Th1 differentiation and function are inhibited in neonates following human metapneumovirus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Review
- Method to Assess Immunosenescent CD8Methods in molecular biology (Clifton, N.J.) · 2025Article
- Monocyte Production of C1q Potentiates CD8American journal of respiratory cell and molecular biology · 2024Article
- PD-1 signaling in neonates restrains CD8Mucosal immunology · 2024Article
- Clinical human metapneumovirus isolates show distinct pathogenesis and inflammatory profiles but similar CD8mSphere · 2024Article
- PD-1 Impairs CD8+ T Cell Granzyme B Production in Aged Mice during Acute Viral Respiratory Infection.ImmunoHorizons · 2023Article
- Terminally exhausted CD8Immunity & ageing : I & A · 2023Article
- Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus.ImmunoHorizons · 2023Article
- Respiratory viruses: New frontiers-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023Article
- LAG-3 Contribution to T Cell Downmodulation during Acute Respiratory Viral Infections.Viruses · 2023Review
- Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8Scientific reports · 2021Article
- Review
- Regulation of Th1 T Cell Differentiation by IronFrontiers in immunology · 2021Article
- Immune Checkpoints in Viral Infections.Viruses · 2020Review
- Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus.Pathogens (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Reinfections with respiratory viruses are common and cause significant clinical illness, yet precise mechanisms governing this susceptibility are ill defined. Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). To determine whether PD-1 contributes to recurrent infection, we first established a model of reinfection by challenging B cell-deficient mice with human metapneumovirus (HMPV) several weeks after primary infection, and found that HMPV replicated to high titers in the lungs. A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). In vitro blockade demonstrated that PD-1 was the dominant inhibitory receptor early after reinfection. In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. Our results indicate that PD-1 signaling may contribute to respiratory virus reinfection and evasion of vaccine-elicited immune responses. These results have important implications for the design of effective vaccines against respiratory viruses.
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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.