ArticleJournal of immunology (Baltimore, Md. : 1950)2014
IL-18 synergizes with IL-7 to drive slow proliferation of naive CD8 T cells by costimulating self-peptide-mediated TCR signals.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Challenges of COPD Patients during the COVID-19 Pandemic.Pathogens (Basel, Switzerland) · 2022Review
- Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b.Nature communications · 2022Article
- Generation of highly proliferative, rejuvenated cytotoxic T cell clones through pluripotency reprogramming for adoptive immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Article
- Expansion of an Unusual Virtual Memory CD8Frontiers in immunology · 2021Article
- T cell receptor and cytokine signal integration in CD8Nature immunology · 2020Article
- Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer.BioMed research international · 2020Review
- Comparative Transcriptomic Analysis Identifies a Range of Immunologically Related Functional Elaborations of Lymph Node Associated Lymphatic and Blood Endothelial Cells.Frontiers in immunology · 2019Article
- Fatty acid metabolism in CD8Immunological reviews · 2018Review
- IL-12 Signals through the TCR To Support CD8 Innate Immune Responses.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Interleukin-7 is required for CD4(+) T cell activation and autoimmune neuroinflammation.Clinical immunology (Orlando, Fla.) · 2015Article
- Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.Immunological reviews · 2015Review
- IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Naive T cell populations are maintained in the periphery at relatively constant levels via mechanisms that control expansion and contraction and are associated with competition for homeostatic cytokines. It has been shown that in a lymphopenic environment naive T cells undergo expansion due, at least in part, to additional availability of IL-7. We have previously found that T cell-intrinsic deletion of TNFR-associated factor (TRAF) 6 (TRAF6ΔT) in mice results in diminished peripheral CD8 T cell numbers. In this study, we report that whereas naive TRAF6ΔT CD8 T cells exhibit normal survival when transferred into a normal T cell pool, proliferation of naive TRAF6ΔT CD8 T cells under lymphopenic conditions is defective. We identified IL-18 as a TRAF6-activating factor capable of enhancing lymphopenia-induced proliferation (LIP) in vivo, and that IL-18 synergizes with high-dose IL-7 in a TRAF6-dependent manner to induce slow, LIP/homeostatic-like proliferation of naive CD8 T cells in vitro. IL-7 and IL-18 act synergistically to upregulate expression of IL-18R genes, thereby enhancing IL-18 activity. In this context, IL-18R signaling increases PI3K activation and was found to sensitize naive CD8 T cells to a model noncognate self-peptide ligand in a way that conventional costimulation via CD28 could not. We propose that synergistic sensitization by IL-7 and IL-18 to self-peptide ligand may represent a novel costimulatory pathway for LIP.
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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.