ArticlePLoS pathogens2019
CD8+ T cells retain protective functions despite sustained inhibitory receptor expression during Epstein-Barr virus infection in vivo.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
- CD20 bispecific T-cell engager depletes B-cell progenitors preventing EBV-associated lymphomagenesis in humanized mice.Blood advances · 2026Article
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- Neuroinflammation as a result of non-neurotropic herpesvirus infection.Immunology and cell biology · 2026Review
- Non-cytolytic re-engineering of a viral vaccine vector enables durable effector-memory T cell immunity by reinforcing type I IFN induction.Molecular therapy. Nucleic acids · 2026Article
- Assessing T-cell responses to Epstein-Barr virus in individuals at risk for nasopharyngeal carcinoma.Infectious agents and cancer · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- CXCR5 identifies stem-like resident memory CD8⁺ T cells enriched for latent EBV specificity in tonsils.Science advances · 2026Article
- Cellular Immunotherapies for Multiple Sclerosis: Mechanistic Insights and Clinical Advances.International journal of molecular sciences · 2026Review
- Humanized Mouse Models of Epstein Barr Virus Infection.Current protocols · 2025Article
- Epstein-Barr virus pathogenesis and emerging control strategies.Nature reviews. Microbiology · 2025Review
- Model Systems of Gammaherpesvirus Infection, Immunity, and Disease.Journal of medical virology · 2025Review
- From Viral Infection to Malignancy: The Dual Threat of EBV and COVID-19 in Cancer Development.Viruses · 2025Review
- Epstein-Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models.Experimental & molecular medicine · 2025Review
- Review
- 2B4/CD244 Signaling in Immune Regulation and Its Role in Infection, Cancer, and Immune Tolerance.ImmunoTargets and therapy · 2025Review
- Epstein-Barr virus infection induces tissue-resident memory T cells in mucosal lymphoid tissues.JCI insight · 2024Article
- THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- An angel or a devil? Current view on the role of CD8Journal of translational medicine · 2024Review
- Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.Frontiers in immunology · 2024Review
- KLRG1-expressing CD8+ T cells are exhausted and polyfunctional in patients with chronic hepatitis B.PloS one · 2024Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epstein Barr virus (EBV) is one of the most ubiquitous human pathogens in the world, persistently infecting more than 90% of the adult human population. It drives some of the strongest human CD8+ T cell responses, which can be observed during symptomatic primary infection known as infectious mononucleosis (IM). Despite high viral loads and prolonged CD8+ T cell stimulation during IM, EBV enters latency and is under lifelong immune control in most individuals that experience this disease. We investigated whether changes in T cell function, as frequently characterized by PD-1 up-regulation, occur during IM due to the prolonged exposure to high antigen levels. We readily detected the expansion of PD-1 positive CD8+ T cells together with high frequencies of Tim-3, 2B4, and KLRG1 expression during IM and in mice with reconstituted human immune system components (huNSG mice) that had been infected with a high dose of EBV. These PD-1 positive CD8+ T cells, however, retained proliferation, cytokine production, and cytotoxic abilities. Multiple subsets of CD8+ T cells expanded during EBV infection, including PD-1+Tim-3+KLRG1+ cells that express CXCR5 and TCF-1 germinal center homing and memory markers, and may also contain BATF3. Moreover, blocking the PD-1 axis compromised EBV specific immune control and resulted in virus-associated lymphomagenesis. Finally, PD-1+, Tim-3+, and KLRG1+ CD8+ T cell expansion coincided with declining viral loads during low dose EBV infection. These findings suggest that EBV infection primes PD-1 positive CD8+ T cell populations that rely on this receptor axis for the efficient immune control of this ubiquitous human tumor virus.
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