ArticleProceedings of the National Academy of Sciences of the United States of America2016
IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Murine IL-2 outperforms human IL-2 in supporting the survival of naïve mouse CD8 T cells in vitro.Life science alliance · 2026Article
- In Vitro Inhibition of STAT5 Signaling Limits CD8+ T-cell Exhaustion and Improves Outcomes in Adoptive T-cell Therapy.Cancer immunology research · 2026Article
- Advances in IL-2 Family Cytokine-Based Cancer Therapies: Overcoming Challenges Through Molecular Engineering and Delivery Strategies.Immune network · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Elderly female CTLs maintain their initial activation and cytotoxicity independent of IL-2.Immunity & ageing : I & A · 2025Article
- Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.Transplantation · 2025Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
- Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-β signal.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A glimpse into the application of the immunomodulatory effect of IL-2 in systemic lupus erythematosus.Frontiers in medicine · 2025Review
- Targeting highly attenuated IL-18 to PD-1 for enhanced anti-tumor activity.Frontiers in immunology · 2025Article
- Article
- Mathematical model for IL-2-based cancer immunotherapy.Mathematical biosciences · 2024Article
- Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.Immunity · 2024Review
- Optimising IL-2 for Cancer Immunotherapy.Immune network · 2024Review
- Article
- An engineered immunocytokine with collagen affinity improves the tumor bioavailability, tolerability, and therapeutic efficacy of IL-2.Cell reports. Medicine · 2023Article
- Stem-like exhausted and memory CD8Nature reviews. Cancer · 2023Review
- In vitro modeling of CD8Science immunology · 2023Article
- Article
- Expansion of circulating stem-like CD8Nature communications · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exhaustion of CD8(+) T cells severely impedes the adaptive immune response to chronic viral infections. Despite major advances in our understanding of the molecular regulation of exhaustion, the cytokines that directly control this process during chronicity remain unknown. We demonstrate a direct impact of IL-2 and IL-15, two common gamma-chain-dependent cytokines, on CD8(+) T-cell exhaustion. Common to both cytokine receptors, the IL-2 receptor β (IL2Rβ) chain is selectively maintained on CD8(+) T cells during chronic lymphocytic choriomeningitis virus and hepatitis C virus infections. Its expression correlates with exhaustion severity and identifies terminally exhausted CD8(+) T cells both in mice and humans. Genetic ablation of the IL2Rβ chain on CD8(+) T cells restrains inhibitory receptor induction, in particular 2B4 and Tim-3; precludes terminal differentiation of highly defective PD-1(hi) effectors; and rescues memory T-cell development and responsiveness to IL-7-dependent signals. Together, we ascribe a previously unexpected role to IL-2 and IL-15 as instigators of CD8(+) T-cell exhaustion during chronic viral infection.
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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.