ArticleJournal of immunology (Baltimore, Md. : 1950)2013
IL-7- and IL-15-mediated TCR sensitization enables T cell responses to self-antigens.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease.PloS one · 2018Trial
- Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15.Cancer immunology research · 2026Article
- Interleukin 15 and autoimmune disorders: pathophysiology, therapeutic potential, and clinical implications.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Diverging effects of tumor necrosis factor inhibitors and conventional synthetic disease-modifying antirheumatic drugs on immunosenescence and inflammageing in rheumatoid arthritis: a cross-sectional analysis.Immunity & ageing : I & A · 2025Article
- Dual T/NK cell engagement via B7-H6-targeted bispecific antibodies and IL-15 eradicates chemo-resistant solid tumors.Frontiers in immunology · 2025Article
- Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis.Journal of translational autoimmunity · 2024Article
- Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.BMC cancer · 2024Article
- IL-15 in T-Cell Responses and Immunopathogenesis.Immune network · 2024Review
- Identification of a unique subset of tissue-resident memory CD4Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.The Biochemical journal · 2022Article
- Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection.Scientific reports · 2022Article
- Significance of bystander T cell activation in microbial infection.Nature immunology · 2022Review
- Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges.Frontiers in oncology · 2022Review
- Protective heterologous T cell immunity in COVID-19 induced by the trivalent MMR and Tdap vaccine antigens.Med (New York, N.Y.) · 2021Article
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- Remodeling Translation Primes CD8Cancer immunology research · 2020Article
- IL7RA genetic variants differentially affect IL-7Rα expression and alternative splicing: a role in autoimmune and infectious diseases?Genes and immunity · 2020Review
- Antitumor T-cell Homeostatic Activation Is Uncoupled from Homeostatic Inhibition by Checkpoint Blockade.Cancer discovery · 2019Article
- IL-15 in autoimmunity and cancer: O-tu-b or not O-tu-b?Nature immunology · 2019Article
- T-cell Activity against AML Improved by Dual-Targeted T Cells Stimulated through T-cell and IL7 Receptors.Cancer immunology research · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of the ERK pathway is intimately involved in determining whether TCR stimulation is productive or induces anergy. T cells from patients with rheumatoid arthritis (RA) have increased ERK responsiveness, which may be relevant for disease pathogenesis. Inflammatory cytokines such as TNF-α did not reproduce the TCR hypersensitivity typical for RA in T cells from healthy individuals. In contrast, priming with the homeostatic cytokines (HCs) IL-7 and IL-15 amplified ERK phosphorylation to TCR stimulation 2- to 3-fold. The underlying mechanism involved a priming of the SOS-dependent amplification loop of RAS activation. The sensitization of the TCR signaling pathway has downstream consequences, such as increased proliferation and preferential Th1 differentiation. Importantly, priming with IL-7 or IL-15 enabled T cell responses to autoantigens associated with RA. Production of HCs is induced in lymphopenic conditions, which have been shown to predispose for autoimmunity and which appear to be present in the preclinical stages of RA. We propose that HCs, possibly induced by lymphopenia, decrease the signaling threshold for TCR activation and are thereby partly responsible for autoimmunity in RA.
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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.