ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 98 citations in OpenAlex.
- Interleukin-21 responses in patients with chronic hepatitis B.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Trial
- Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression.The Journal of clinical investigation · 2014Trial
- Modulation of pulmonary IL-21 expression during latent TB and M. tuberculosis/SIV coinfection.JCI insight · 2026Article
- Therapeutic Targeting of Viral Myocarditis with Natural Products and Herbal Medicines: From Immune-Inflammatory Mechanisms to Clinical Translation.Journal of inflammation research · 2026Review
- IL-21 isoform transgenic mice spontaneously develop mammary tumors: possible involvement of IL-21-induced osteopontin expression in tumorigenesis.Frontiers in immunology · 2026Article
- Advances in host-directed therapy for tuberculosis and HIV coinfection: enhancing immune responses.Trends in microbiology · 2025Review
- JAK-STAT pathway, type I/II cytokines, and new potential therapeutic strategy for autoimmune bullous diseases: update on pemphigus vulgaris and bullous pemphigoid.Frontiers in immunology · 2025Review
- Deciphering the potential role of PGRN in regulating CD8Cell death discovery · 2024Article
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Review
- Restriction of Viral Replication, Rather than T Cell Immunopathology, Drives Lethality in Murine Norovirus CR6-Infected STAT1-Deficient Mice.Journal of virology · 2022Article
- Gnawing Between Cells and Cells in the Immune System: Friend or Foe? A Review of Trogocytosis.Frontiers in immunology · 2022Review
- Lipophagy confers a key metabolic advantage that ensures protective CD8A T-cell responses against HIV-1.Autophagy · 2021Article
- Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8Immune network · 2021Article
- Interleukin-21 in Viral Infections.International journal of molecular sciences · 2021Review
- HIV-1 infection and the lack of viral control are associated with greater expression of interleukin-21 receptor on CD8+ T cells.AIDS (London, England) · 2021Article
- TargetingFrontiers in immunology · 2021Article
- IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice.Frontiers in immunology · 2021Article
- IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection.Science immunology · 2020Article
- Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation.Blood advances · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
CD4 T cell help plays an important role in promoting CD8 T cell immunity to pathogens. In models of infection with vaccinia virus (VV) and Listeria monocytogenes, CD4 T cell help is critical for the survival of activated CD8 T cells during both the primary and memory recall responses. Still unclear, however, is how CD4 T cell help promotes CD8 T cell survival. In this study, we first showed that CD4 T cell help for the CD8 T cell response to VV infection was mediated by IL-21, a cytokine produced predominantly by activated CD4 T cells, and that direct action of IL-21 on CD8 T cells was critical for the VV-specific CD8 T cell response in vivo. We next demonstrated that this intrinsic IL-21 signaling was essential for the survival of activated CD8 T cells and the generation of long-lived memory cells. We further revealed that IL-21 promoted CD8 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 pathways and subsequent upregulation of the prosurvival molecules Bcl-2 and Bcl-x(L). These results identify a critical role for intrinsic IL-21 signaling in CD8 T cell responses to an acute viral infection in vivo and may help design effective vaccine strategies.
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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.