ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Regulation of antiviral immunity by PD-1 during respiratory syncitial virus infection and upon vaccination.iScience · 2026Article
- Immune cell disorder in viral pneumonia.Journal of translational medicine · 2026Review
- Mechanistic insights and emerging applications of human metapneumovirus (HMPV) treatment: From molecular design to translational immunity.Folia microbiologica · 2026Review
- Dimethyl Sulfoxide Modulates T Cell-Mediated Immunity to Attenuate Influenza A Virus Infection.Journal of inflammation research · 2026Article
- Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity.Frontiers in immunology · 2026Review
- Human metapneumovirus: understanding the molecular mechanisms and pathology of infection.Journal of virology · 2025Review
- Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Method to Assess Immunosenescent CD8Methods in molecular biology (Clifton, N.J.) · 2025Article
- Genetic absence of PD-L1 does not restore CD8Journal of virology · 2024Article
- Monocyte Production of C1q Potentiates CD8American journal of respiratory cell and molecular biology · 2024Article
- PD-1 signaling in neonates restrains CD8Mucosal immunology · 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
- Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?Cancers · 2021Review
- LAG-3: from molecular functions to clinical applications.Journal for immunotherapy of cancer · 2020Review
- Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus.Pathogens (Basel, Switzerland) · 2020Review
- Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue-Resident Memory T Cells during H5N1 Infection.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections.
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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.