ArticleJournal of virology2016
Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection.
Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.BMC microbiology · 2021Trial
- A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.Molecular & cellular proteomics : MCP · 2025Review
- Immunomodulatory behavior of CircRNAs in tumor microenvironment.Oncology research · 2025Review
- HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.Communications biology · 2024Article
- mRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity.Cell reports. Medicine · 2024Article
- Advances in macrophage and T cell metabolic reprogramming and immunotherapy in the tumor microenvironment.PeerJ · 2024Article
- The metabolic consequences of HIV/TB co-infection.BMC infectious diseases · 2023Article
- The TLR7/IRF-5 axis sensitizes memory CD4+ T cells to Fas-mediated apoptosis during HIV-1 infection.JCI insight · 2023Article
- Antigen-specific cytokine profiles for pulmonaryFrontiers in immunology · 2023Article
- Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry.Journal for immunotherapy of cancer · 2022Article
- Fighting in a wasteland: deleterious metabolites and antitumor immunity.The Journal of clinical investigation · 2022Review
- Immunopathogenesis in HIV-associated pediatric tuberculosis.Pediatric research · 2022Review
- Defining the AHR-regulated transcriptome in NK cells reveals gene expression programs relevant to development and function.Blood advances · 2021Article
- The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies.International journal of molecular sciences · 2021Review
- The effects of aging on host resistance and disease tolerance to SARS-CoV-2 infection.The FEBS journal · 2021Review
- Role of kynurenine in promoting the generation of exhausted CD8American journal of translational research · 2021Article
- Immune metabolism in PD-1 blockade-based cancer immunotherapy.International immunology · 2021Review
- Abnormal Tryptophan Metabolism in HIV andFrontiers in microbiology · 2021Review
- Metabolomics as a Tool to Investigate HIV/TB Co-Infection.Frontiers in molecular biosciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledEarly HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant N-acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection. IMPORTANCE: The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection.
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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.