ArticleImmunity2011
Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8(+) T cells.
Article in Immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers.
What it found
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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
280 citing papers in PubMed, 402 citations in OpenAlex.
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- Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination.The Journal of clinical investigation · 2020Trial
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
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- ILC2s and their immune checkpoints in the antitumor response.Journal for immunotherapy of cancer · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Human DNA levels in feces reflect gut inflammation and associate with presence of gut species in IBD patients across the age spectrum.Microbiome · 2026Article
- Targeting epigenetic regulators to boost T cell immunotherapy against cancer.Cell & bioscience · 2026Review
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Programmed cell death-1: from a T-cell immune checkpoint to a regulator of Natural Killer cell biology.Frontiers in cell and developmental biology · 2026Review
- Epigenetic regulation of T cell exhaustion in cancer.Nature reviews. Cancer · 2026Review
- From exhaustion to functional cure: frontiers in reversing HBV-specific T-cell immunity.Frontiers in immunology · 2026Review
- Traditional Chinese Medicine in Chronic Hepatitis B: Integrating Antiviral Effects and Immune Modulation in the Context of T Cell Exhaustion.Drug design, development and therapy · 2026Review
- Macrophages regulate PD-1 and CTLA-4 expression on ILC2s and their responsiveness in the tumor microenvironment.Cellular & molecular immunology · 2025Article
- Aging and immunity: the age-old tango.Genes & development · 2025Review
- Review
- Review
- The epigenetic landscape of fate decisions in T cells.Nature immunology · 2025Review
220 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Functionally exhausted T cells have high expression of the PD-1 inhibitory receptor, and therapies that block PD-1 signaling show promise for resolving chronic viral infections and cancer. By using human and murine systems of acute and chronic viral infections, we analyzed epigenetic regulation of PD-1 expression during CD8(+) T cell differentiation. During acute infection, naive to effector CD8(+) T cell differentiation was accompanied by a transient loss of DNA methylation of the Pdcd1 locus that was directly coupled to the duration and strength of T cell receptor signaling. Further differentiation into functional memory cells coincided with Pdcd1 remethylation, providing an adapted program for regulation of PD-1 expression. In contrast, the Pdcd1 regulatory region was completely demethylated in exhausted CD8(+) T cells and remained unmethylated even when virus titers decreased. This lack of DNA remethylation leaves the Pdcd1 locus poised for rapid expression, potentially providing a signal for premature termination of antiviral functions.
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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.