ArticleJournal of immunology (Baltimore, Md. : 1950)2017
IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 119 citations in OpenAlex.
- Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer.Nature communications · 2025Trial
- Murine IL-2 outperforms human IL-2 in supporting the survival of naïve mouse CD8 T cells in vitro.Life science alliance · 2026Article
- Regulation of follicular helper T cell subset differentiation in health and disease.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Tumor-targeted IL2 promotes specific CD8Journal of experimental & clinical cancer research : CR · 2026Article
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
- Ubiquitous Expression ofLife (Basel, Switzerland) · 2025Article
- Regulation of TCR-induced Transcriptional Kinetics by Interleukin 2-inducible T Cell Kinase (ITK) in CD8bioRxiv : the preprint server for biology · 2025Article
- Molecular endotypes in sepsis: integration of multicohort transcriptomics based on RNA sequencing.Journal of intensive care · 2025Article
- An engineered viral protein activates STAT5 to prevent T cell suppression.Science immunology · 2025Article
- An early precursor CD8Nature · 2025Article
- Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study.Journal for immunotherapy of cancer · 2025Article
- Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.Nature communications · 2025Article
- Flotillin-2 dampens T cell antigen sensitivity and functionality.JCI insight · 2024Article
- Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHD.The Journal of clinical investigation · 2024Article
- Low-affinity CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- Cbl-b mitigates the responsiveness of naive CD8Science signaling · 2024Article
- Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing.European journal of immunology · 2024Article
- Nonactivated and IL-7 cultured CD19-specific CAR T cells are enriched in stem cell phenotypes and functionally superior.Blood advances · 2024Article
- NKG2D receptor signaling shapes T cell thymic education.Journal of leukocyte biology · 2024Article
- Survival and division fate programs are preserved but retuned during the naïve to memory CD8Immunology and cell biology · 2024Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Lymphocytes integrate Ag and cytokine receptor signals to make cell fate decisions. Using a specific reporter of TCR signaling that is insensitive to cytokine signaling, Nur77-eGFP, we identify a sharp, minimal threshold of cumulative TCR signaling required for proliferation in CD4 and CD8 T cells that is independent of both Ag concentration and affinity. Unexpectedly, IL-2 reduces this threshold in CD8 but not CD4 T cells, suggesting that integration of multiple mitogenic inputs may alter the minimal requirement for TCR signaling in CD8 T cells. Neither naive CD4 nor naive CD8 T cells are responsive to low doses of IL-2. We show that activated CD8 T cells become responsive to low doses of IL-2 more quickly than CD4 T cells, and propose that this relative delay in turn accounts for the differential effects of IL-2 on the minimal TCR signaling threshold for proliferation in these populations. In contrast to Nur77-eGFP, c-Myc protein expression integrates mitogenic signals downstream of both IL-2 and the TCR, yet marks an invariant minimal threshold of cumulative mitogenic stimulation required for cell division. Our work provides a conceptual framework for understanding the regulation of clonal expansion of CD8 T cells by subthreshold TCR signaling in the context of mitogenic IL-2 signals, thereby rendering CD8 T cells exquisitely dependent upon environmental cues. Conversely, CD4 T cell proliferation requires an invariant minimal intensity of TCR signaling that is not modulated by IL-2, thereby restricting responses to low-affinity or low-abundance self-antigens even in the context of an inflammatory milieu.
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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.