ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces CD4+ T Cell Anergy via GRAIL.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 36 citations in OpenAlex.
- Human memory CD4bioRxiv : the preprint server for biology · 2026Article
- Regulatory roles of E3 ubiquitin ligase RNF128 in inflammatory diseases and tumors.Journal of Cancer · 2026Review
- Finding and filling the knowledge gaps in mechanisms of T cell-mediated TB immunity to inform vaccine design.Nature reviews. Immunology · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Extracellular vesicles in bacterial and fungal diseases - Pathogenesis to diagnostic biomarkers.Virulence · 2023Review
- Impact of Mycobacterium tuberculosis Glycolipids on the CD4+ T Cell-Macrophage Immunological Synapse.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Immunological hyporesponsiveness in tuberculosis: The role of mycobacterial glycolipids.Frontiers in immunology · 2022Review
- In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlyingFrontiers in microbiology · 2022Article
- The Immunological Synapse: An Emerging Target for Immune Evasion by Bacterial Pathogens.Frontiers in immunology · 2022Review
- The knowns and unknowns of latent Mycobacterium tuberculosis infection.The Journal of clinical investigation · 2021Review
- High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids.Frontiers in immunology · 2021Article
- Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?Frontiers in microbiology · 2021Review
- Changes in T-lymphocyte subsets and risk factors in human immunodeficiency virus-negative patients with active tuberculosis.Infection · 2020Article
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- Helminth-induced Th2 cell dysfunction is distinct from exhaustion and is maintained in the absence of antigen.PLoS neglected tropical diseases · 2019Article
- Mycobacterial mannose-capped lipoarabinomannan: a modulator bridging innate and adaptive immunity.Emerging microbes & infections · 2019Review
- Mechanisms of M. tuberculosis Immune Evasion as Challenges to TB Vaccine Design.Cell host & microbe · 2018Review
- Potential Effect of Statins onJournal of immunology research · 2018Review
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit CD4(+) T cell activation by downregulating the phosphorylation of key proximal TCR signaling molecules: Lck, CD3ζ, ZAP70, and LAT. Inhibition of proximal TCR signaling can result in T cell anergy, in which T cells are inactivated following an Ag encounter, yet remain viable and hyporesponsive. We tested whether mannose-capped lipoarabinomannan (LAM)-induced inhibition of CD4(+) T cell activation resulted in CD4(+) T cell anergy. The presence of LAM during primary stimulation of P25 TCR-transgenic murine CD4(+) T cells with M. tuberculosis Ag85B peptide resulted in decreased proliferation and IL-2 production. P25 TCR-transgenic CD4(+) T cells primed in the presence of LAM also exhibited decreased response upon restimulation with Ag85B. The T cell anergic state persisted after the removal of LAM. Hyporesponsiveness to restimulation was not due to apoptosis, generation of Foxp3-positive regulatory T cells, or inhibitory cytokines. Acquisition of the anergic phenotype correlated with upregulation of gene related to anergy in lymphocytes (GRAIL) protein in CD4(+) T cells. Inhibition of human CD4(+) T cell activation by LAM also was associated with increased GRAIL expression. Small interfering RNA-mediated knockdown of GRAIL before LAM treatment abrogated LAM-induced hyporesponsiveness. In addition, exogenous IL-2 reversed defective proliferation by downregulating GRAIL expression. These results demonstrate that LAM upregulates GRAIL to induce anergy in Ag-reactive CD4(+) T cells. Induction of CD4(+) T cell anergy by LAM may represent one mechanism by which M. tuberculosis evades T cell recognition.
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.