ArticleJCI insight2021
Inflammatory signals are sufficient to elicit TOX expression in mouse and human CD8+ T cells.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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
32 citing papers in PubMed, 40 citations in OpenAlex.
- NF-κB-activated fibroblasts orchestrate inflammaging and emergence of pro-inflammatory granzyme KImmunity · 2026Article
- PD-1 regulates latent effector differentiation of thymic cytotoxic CD8Nature communications · 2026Article
- TOX drives CD4Nature immunology · 2026Article
- Human lung γδ T cells maintain functionality during inflammatory lung disease.bioRxiv : the preprint server for biology · 2026Article
- Tissue-specific adaptation of human T cells is preserved during tissue inflammation.bioRxiv : the preprint server for biology · 2026Article
- IL-4-STAT6 signaling delays protective CD8Nature immunology · 2026Article
- Anti-CD3 mAb treatment reshapes infiltrating T and β cells in the islets in autoimmune diabetes.JCI insight · 2026Article
- Immunosuppressive cell populations as potential drivers of extrinsic immune checkpoint inhibition resistance in clear cell renal cell carcinoma.Oncology reviews · 2026Review
- Fibroblast orchestration of inflammaging via NF-kB activation.bioRxiv : the preprint server for biology · 2025Article
- Cytokine and metabolite networks shape T cell residency and functionality at the term human maternal-fetal interface.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immunometabolic Targets in CD8Liver cancer · 2025Review
- Six degrees of TGFβ.Nature immunology · 2025Article
- IL-2 immunotherapy rescues irradiation-induced T cell exhaustion in mouse colon cancer.iScience · 2025Article
- TOX, through a glass, darkly.Frontiers in immunology · 2025Review
- The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Steady-state, therapeutic, and helminth-induced IL-4 compromise protective CD8 T cell bystander activation.bioRxiv : the preprint server for biology · 2024Article
- Immunotherapy for colorectal cancer: insight from inherited genetics.Trends in cancer · 2024Review
- TIM-3Science immunology · 2024Article
- Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.Communications biology · 2024Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
T cell receptor (TCR) stimulation leads to the expression of the transcription factor thymocyte selection-associated high-mobility group box (TOX). Prolonged TCR signaling, such as encountered during chronic infections or in tumors, leads to sustained TOX expression, which is required for the induction of a state of exhaustion or dysfunction. Although CD8+ memory T (Tmem) cells in mice typically do not express TOX at steady state, some human Tmem cells express TOX but appear fully functional. This seeming discrepancy between mouse and human T cells has led to the speculation that TOX is differentially regulated between these species, which could complicate the interpretation of preclinical mouse model studies. We report here that, similar to TCR-mediated signals, inflammatory cytokines are also sufficient to increase TOX expression in human and mouse Tmem cells. Thus, TOX expression is controlled by the environment, which provides an explanation for the different TOX expression patterns encountered in T cells isolated from specific pathogen-free laboratory mice versus humans. Finally, we report that TOX is not necessary for cytokine-driven expression of programmed cell death 1. Overall, our data highlight that the mechanisms regulating TOX expression are conserved across species and indicate that TOX expression reflects a T cell's activation state and does not necessarily correlate with T cell dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.