ArticleThe Journal of experimental medicine2016
High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 170 citations in OpenAlex.
- PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation.The Journal of clinical investigation · 2018Trial
- Lineage-specific immune checkpoint dynamics define a context-dependent regulatory framework with translational relevance in human γδ T cells.Journal of translational medicine · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- New insights into progenitor exhausted T cell populations.Nature reviews. Immunology · 2026Article
- Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.Nature communications · 2026Article
- Site-1 protease mediated GPC processing is required for persistence of LCMV Clone 13.Npj viruses · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Upregulation of TNFR2 Precedes TOX Expression by Exhausted T cells and Restricts Antitumor and Antiviral Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma.Experimental hematology & oncology · 2026Article
- Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner.Clinical and experimental immunology · 2026Article
- Intermittent Tacrolimus Treatment Delays CD8+ Tumor-Infiltrating Lymphocyte Exhaustion and Enhances PD1 Blockade Therapy in Melanoma-Bearing Mice.Journal of immunology research · 2026Article
- Lpar5 regulates the CD8 T-cell response to persistent virus infection by altering exhaustion programming, survival, and NK receptor expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Upregulation of PD-1 on Peripheral T cells Subsets is Associated with Parkinson's Disease.Molecular neurobiology · 2025Article
- Lymph nodes fuel KLF2-dependent effector CD8Nature immunology · 2025Article
- Performance Evaluation of a HBsAg-Specific Immunoadsorbent Based on a Humanized Anti-HBsAg Monoclonal Antibody.Biomedicines · 2025Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
- High antigen burden drives CD8+ T cell dysfunction in a mouse model of chronic hepatitis B virus infection.Journal of virology · 2025Article
- Splenic fibroblastic reticular cells orchestrate dendritic cell maturation and facilitate CD8Science advances · 2025Article
- In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation.Nature communications · 2025Article
58 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
9 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition of this chronic phenotype and how it impacts T cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing chronic lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that T cell differentiation and acquisition of a chronic or exhausted phenotype depend critically on the frequency of T cell receptor (TCR) engagement and less significantly on the strength of TCR stimulation. In fact, we noted that low-level antigen exposure promotes the formation of T cells with an acute phenotype in chronic infections. Unexpectedly, we found that T cell populations with an acute or chronic phenotype are maintained equally well in chronic infections and undergo comparable primary and secondary expansion. Thus, our observations contrast with the view that T cells with a typical chronic infection phenotype are severely functionally impaired and rapidly transition into a terminal stage of differentiation. Instead, our data unravel that T cells primarily undergo a form of phenotypic and functional differentiation in the early phase of a chronic LCMV infection without inheriting a net survival or expansion deficit, and we demonstrate that the acquired chronic phenotype transitions into the memory T cell compartment.
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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.