ArticleThe Journal of experimental medicine2003
Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 233 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
233 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Promising effects of parasite-derived compounds on tumor regression: a systematic review of in vitro and in vivo studies.Environmental science and pollution research international · 2022Pooled it
- Beyond cold to hot: oncolytic virotherapy as the next cornerstone of immuno-oncology.Nature reviews. Clinical oncology · 2026Review
- Non-canonical clonal expansion of autoreactive CD8Cell insight · 2026Article
- Combinatorial in situ cancer vaccines: unlocking broad and enhanced antitumor responses.Signal transduction and targeted therapy · 2026Review
- Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- CD8 T Cell Sensing of Type I Interferon Impacts Anergy.European journal of immunology · 2026Article
- Combined administration of interleukin-2 and 18 with anti-PD-L1 antibody induces CCL5-positive CD8 T cells to suppress liver tumors.PNAS nexus · 2026Article
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- DNA damage in macrophages drives immune autoreactivity via nuclear antigen presentation.Nature aging · 2026Article
- Delayed type I interferon response and the subsequent out-of-sequence cytokine signal inhibit T cell induction in non-surviving Ebola virus-infected patients.Frontiers in immunology · 2026Article
- Microglial state transitions are constrained by developmental and metabolic checkpoints.Frontiers in cellular neuroscience · 2026Review
- Advances in IL-2-based cancer immunotherapy and the synergistic role of stem-like CD8Frontiers in immunology · 2026Review
- Pathogenesis of Chronic Rejection: Graft Endothelial Cell Trans-presentation of IL-15 Connects Alloantibody- and Cell-Mediated Steps in Allograft Vasculopathy.Results and problems in cell differentiation · 2026Review
- Review
- 2240 nm NIR-IV Photodynamic Therapy Can Reverse Ineffective Anti-OX40 Cancer Immunotherapy to Become Effective.ACS nano · 2025Article
- T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responses.Journal of virology · 2025Article
- Antioxidant Cerium Oxide Nanoparticle Coatings Impart Immunomodulatory Effects by Suppressing Antigen-Specific Cytotoxic T Cell Activation.Journal of biomedical materials research. Part A · 2025Article
- Molecular insights into T cell development, activation and signal transduction (Review).Biomedical reports · 2025Review
- Harnessing extracellular vesicle-mediated crosstalk between T cells and cancer cells for therapeutic applications.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Bacterial outer membrane vesicles OMV-LL for delivery of neoantigen mRNA to induce anti-HCC therapy.Frontiers in immunology · 2025Article
173 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Activation of naive CD8 T cells to undergo clonal expansion and develop effector function requires three signals: (a) Ag, (b) costimulation, and (c) IL-12 or adjuvant. The requirement for the third signal to stimulate Ag-dependent proliferation is variable, making the greatest contribution when Ag levels are low. At high Ag levels, extensive proliferation can occur in vitro or in vivo in the absence of a third signal. However, despite having undergone the same number of divisions, cells that expand in the absence of a third signal fail to develop cytolytic effector function. Thus, proliferation and development of cytolytic function can be fully uncoupled. Furthermore, these cells are rendered functionally tolerant in vivo, in that subsequent restimulation with a potent stimulus results in limited clonal expansion, impaired IFN-gamma production, and no cytolytic function. Thus, the presence or absence of the third signal appears to be a critical variable in determining whether stimulation by Ag results in tolerance versus development of effector function and establishment of a responsive memory population.
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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.