ArticleCytokine2006
Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal.
Article in Cytokine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes.Journal of translational medicine · 2026Pooled it
- ATF7ip Inhibits the Tumor Immune Response by Promoting Terminal CD8+ T-cell Exhaustion.Cancer immunology research · 2026Article
- HIV-seq reveals gene expression differences between HIV-transcribing cells from viremic and suppressed people with HIV.Nature communications · 2026Article
- Immune evolution and therapeutic vulnerabilities in thyroid cancer: from inflammation to immune escape.Frontiers in immunology · 2026Review
- Regulation of Granzymes A and B by High-Risk HPV: Impact on Immune Evasion and Carcinogenesis.Viruses · 2025Review
- The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.Experimental hematology & oncology · 2024Review
- Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes.Discovery immunology · 2024Review
- IL-15-induced CD38Clinical & translational immunology · 2024Article
- FKBP5 associated CD8 T cell infiltration is a novel prognostic biomarker in luminal B breast cancer.The Journal of international medical research · 2023Article
- The mRNA expression and secretion of granzyme B are up-regulated via the histamine H2 receptor in human CD4Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Article
- Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies.Nature communications · 2022Article
- NKTR-255 is a polymer-conjugated IL-15 with unique mechanisms of action on T and natural killer cells.The Journal of clinical investigation · 2021Article
- Circulating mature granzyme B+ T cells distinguish Crohn's disease-associated axial spondyloarthritis from axial spondyloarthritis and Crohn's disease.Arthritis research & therapy · 2021Article
- Nicotine exhausts CD8Cancer immunology, immunotherapy : CII · 2021Article
- Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction.Environmental health and preventive medicine · 2021Article
- Granzyme B Inhibition by Tofacitinib Blocks the Pathology Induced by CD8 T Cells in Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2021Article
- The Ugly Duckling Turned to Swan: A Change in Perception of Bystander-Activated Memory CD8 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma.Frontiers in veterinary science · 2021Article
- NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The purpose of these studies was to determine the minimal requirements to induce granzyme B, cytotoxic granules and perforin-dependent lytic capacity. To our surprise, both IL-2 and IL-15 induced not only proliferation, but also profound granzyme B and lytic capacity from CD8+ T cells in the absence of antigen or TCR-stimulation. Mouse splenocytes were incubated with mouse r-IL-2 or r-IL-15 for three days, tested by anti-CD3 redirected lysis and examined for intracellular granzyme B and for T cell activation markers. With 10(-8) M IL-2 or IL-15, there was excellent lytic activity at 1:1 effector to target ratios mediated by T cells from wild-type but not from perforin-gene-ablated mice, consistent with multiclonal activation. Lower interleukin concentrations induced less lytic activity. Granzyme B was undetectable on day 0, and greatly elevated on day 3 in CD44hi CD8+ T cells as detected by flow cytometry. Cytokines alone elevated the granzyme B as much as concanavalin A combined with the cytokines. Some ex vivo CD8+ T cells were CD122+, as were the cultured granzyme B+ cells, thus both populations had low-affinity receptors for the interleukins. Only some of the activated cells were proliferating as detected by CFSE labeling. When the cytokines were withdrawn, the cells lost lytic activity within 24 h and then within the next 24 h, died. Our results suggest that high concentrations of either IL-2 or IL-15 will activate the lytic capacity and granzyme B expression of many T cells and that antigen recognition is not required.
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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.