ArticleJournal of immunology (Baltimore, Md. : 1950)2009
ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-responsive human T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions.PLoS pathogens · 2012Trial
- Immunoregulation by ESAT-6: From Pathogenesis of Tuberculosis to Potential Anti-Inflammatory and Anti-Rejection Application.Pharmaceuticals (Basel, Switzerland) · 2025Review
- An integrative and comprehensive analysis of blood transcriptomes combined with machine learning models reveals key signatures for tuberculosis diagnosis and risk stratification.Frontiers in microbiology · 2025Article
- Impact of anti-TB drugs on modulations of T-cell-receptor-mediated signaling events in TB pleurisy patients.Frontiers in immunology · 2025Review
- A multi-epitope vaccine incorporating adhesin-derived antigens protects againstFrontiers in immunology · 2025Article
- Review
- From pathogenesis to antigens: the key to shaping the future of TB vaccines.Frontiers in immunology · 2024Review
- ESAT-6 protein suppresses allograft rejection by inducing CD4Frontiers in immunology · 2024Article
- Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study.PLOS global public health · 2023Article
- Different modalities of host cell death and their impact onAmerican journal of physiology. Cell physiology · 2022Review
- Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection.iScience · 2022Article
- Exploring modulations in T-cell receptor-mediated T-cell signaling events in systemic circulation and at local disease site of patients with tubercular pleural effusion: An attempt to understand tuberculosis pathogenesis at the local disease site.Frontiers in medicine · 2022Article
- Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward.PLoS pathogens · 2021Review
- Vaccination Strategies Against Mycobacterium tuberculosis: BCG and Beyond.Advances in experimental medicine and biology · 2021Article
- Subunit Vaccine ESAT-6:c-di-AMP Delivered by Intranasal Route Elicits Immune Responses and Protects AgainstFrontiers in cellular and infection microbiology · 2021Article
- Quantitative investigation of factors relevant to the T cell spot test for tuberculosis infection in active tuberculosis.BMC infectious diseases · 2019Article
- An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.NPJ vaccines · 2019Article
- EXPRESSION OF IMMUNOGLOBULIN, GRANZYME-B AND PERFORIN AGAINST Ag85A AND Ag85B PROTEINS OF MYCOBACTERIUM TUBERCULOSIS IN BALB/C MICE.African journal of infectious diseases · 2019Article
- Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.Journal of clinical microbiology · 2018Article
- The stringent response and Mycobacterium tuberculosis pathogenesis.Pathogens and disease · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The Mycobacterium tuberculosis early secreted Ag of 6 kDa (ESAT-6) is a potent Ag for human T cells and is a putative vaccine candidate. However, ESAT-6 also contributes to virulence in animal models, mediates cellular cytolysis, and inhibits IL-12 production by mononuclear phagocytes. We evaluated the effects of ESAT-6 and its molecular chaperone, culture filtrate protein of 10 kDa (CFP10), on the capacity of human T cells to produce IFN-gamma and proliferate in response to TCR activation. Recombinant ESAT-6, but not CFP10, markedly inhibited IFN-gamma production by T cells stimulated with M. tuberculosis or with the combination of anti-CD3 and anti-CD28, in a dose-dependent manner. ESAT-6 also inhibited T cell production of IL-17 and TNF-alpha but not IL-2. Preincubation of ESAT-6 with CFP10 under conditions that favor dimer formation did not affect inhibition of IFN-gamma. ESAT-6 decreased IFN-gamma transcription and reduced expression of the transcription factors, ATF-2 and c-Jun, which normally bind to the IFN-gamma proximal promoter and stimulate mRNA expression. ESAT-6 inhibited T cell IFN-gamma secretion through mechanisms that did not involve cellular cytotoxicity or apoptosis. ESAT-6, but not CFP10, bound to T cells and inhibited expression of early activation markers without reducing activation of ZAP70. We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70.
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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.