ArticleJournal of immunology (Baltimore, Md. : 1950)2016
A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 47 citations in OpenAlex.
- The Number of Donor-Specific IL-21 Producing Cells Before and After Transplantation Predicts Kidney Graft Rejection.Frontiers in immunology · 2019Trial
- β-Catenin stabilization protects against alveolar hemorrhage through amphiregulin- and BATF-mediated Tregs.JCI insight · 2026Article
- Beyond priming: a sequential, feedback-guided adjuvant framework for therapeutic cancer peptide vaccines in immunologically cold tumors.Frontiers in immunology · 2026Review
- Metabolic Checkpoints in CD8International journal of biological sciences · 2026Review
- Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1Nature immunology · 2025Article
- Keeping it local: how CD8 TRMs regulate viral and cancer immunity.Frontiers in immunology · 2025Review
- Inflammatory response signature score model for predicting immunotherapy response and pan-cancer prognosis.Computational and structural biotechnology journal · 2024Article
- Ablation ofiScience · 2024Article
- Gluten induces rapid reprogramming of natural memory αβ and γδ intraepithelial T cells to induce cytotoxicity in celiac disease.Science immunology · 2023Article
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
- CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1Cancer immunology, immunotherapy : CII · 2022Article
- Emerging Strategies in TCR-Engineered T Cells.Frontiers in immunology · 2022Review
- Next-generation cytokines for cancer immunotherapy.Antibody therapeutics · 2021Review
- Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8Science translational medicine · 2021Article
- A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Potential anti-EBV effects associated with elevated interleukin-21 levels: a case report.BMC infectious diseases · 2020Article
- Resident Memory T Cells and Their Role within the Liver.International journal of molecular sciences · 2020Review
- IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection.Science immunology · 2020Article
- Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells.JCI insight · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The activation of naive CD8 T cells typically results in the formation of effector cells (TE) as well as phenotypically distinct memory cells that are retained over time. Memory CD8 T cells can be further subdivided into central memory, effector memory (TEM), and tissue-resident memory (TRM) subsets, which cooperate to confer immunological protection. Using mixed bone marrow chimeras and adoptive transfer studies in which CD8 T cells either do or do not express IL-21R, we discovered that under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumulation of TE/TEM populations. The inability to perceive IL-21 signals under competitive conditions also resulted in lower levels of TRM phenotype cells and reduced expression of granzyme B in the small intestine. IL-21 differentially promoted the expression of the chemokine receptor CX3CR1 and the integrin α4β7 on CD8 T cells primed in vitro and on circulating CD8 T cells in the mixed bone marrow chimeras. The requirement for IL-21 to establish CD8 TE/TEM and TRM subsets was overcome by acute lymphocytic choriomeningitis virus infection; nevertheless, memory virus-specific CD8 T cells remained dependent on IL-21 for optimal accumulation in lymphopenic environments. Overall, this study reveals a context-dependent role for IL-21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and 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.