ArticleThe Journal of experimental medicine1997
Single cell analysis reveals regulated hierarchical T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4+ T cells.
Article in The Journal of experimental medicine, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 220 citations in OpenAlex.
- Interferon-gamma administration after abdominal surgery rescues antigen-specific helper T cell immune reactivity.Clinical and experimental immunology · 2001Trial
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- The quantum model of T-cell activation: Revisiting immune response theories.Scandinavian journal of immunology · 2024Article
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- Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens.Transplantation direct · 2021Article
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- Soluble trivalent engagers redirect cytolytic T cell activity toward tumor endothelial marker 1.Cell reports. Medicine · 2021Article
- A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand.Science advances · 2021Article
- Exploiting Single-Cell Tools in Gene and Cell Therapy.Frontiers in immunology · 2021Review
- Human CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes.Frontiers in immunology · 2020Article
- Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor-engineered T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance.Immunological reviews · 2019Review
- Biomaterial-Based Activation and Expansion of Tumor-Specific T Cells.Frontiers in immunology · 2019Review
- Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology.Frontiers in immunology · 2018Review
- Transcriptome Analysis of Mycobacteria-Specific CD4Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Heterogeneity assessment of functional T cell avidity.Scientific reports · 2017Article
- M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8Frontiers in immunology · 2017Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell receptor (TCR) recognition of peptide-major histocompatibility complex antigens can elicit a diverse array of effector activities. Here we simultaneously analyze TCR engagement and the production of multiple cytokines by individual cells in a clonal Th1 CD4(+) cell population. Low concentrations of TCR ligand elicit only interferon-gamma (IFN-gamma) production. Increasing ligand recruits more cells into the IFN-gamma+ pool, increases IFN-gamma produced per cell, and also elicits IL-2, but only from cells already making IFN-gamma. Most cells producing only IFN-gamma show less TCR downmodulation than cells producing both cytokines, consistent with a requirement for more TCR signaling to elicit IL-2 than to evoke IFN-gamma synthesis. These studies emphasize the hierarchical organization of TCR signaling thresholds for induction of distinct cytokine responses, and demonstrate that this threshold phenomenon applies to individual cells. The existence of such thresholds suggests that antigen dose may dictate not only the extent, but also the quality of an immune response, by altering the ratios of the cytokines produced by activated T cells. The quantitative relationships in this response hierarchy change in response to costimulation through CD28 or LFA-1, as well as the differentiation state of the lymphocyte, explaining how variations in these parameters in the face of a fixed antigen load can qualitatively influence immune outcomes. Finally, although the IFN-gamma/IL-2 hierarchy is seen with most cells, among cells with the greatest TCR downmodulation, some produce only IFN-gamma and not IL-2, and the amount of IFN-gamma exceeds that in double producers. Thus, these single cell analyses also provide clear evidence of nonquantitative intraclonal heterogeneity in cytokine production by long-term Th1 cells, indicating additional complexity of T cell function during immune responses.
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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.