ArticlePLoS pathogens2011
Suboptimal activation of antigen-specific CD4+ effector cells enables persistence of M. tuberculosis in vivo.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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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.
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Who cites it
101 citing papers in PubMed, 145 citations in OpenAlex.
- Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.Cell host & microbe · 2017Trial
- Human memory CD4bioRxiv : the preprint server for biology · 2026Article
- HowVaccines · 2026Review
- Cytotoxic granules and effector molecules from immune cells in tuberculosis: Mechanisms of host defense and therapeutic potential.Virulence · 2025Review
- Human CD4+ T cells recognize Mycobacterium tuberculosis-infected macrophages amid broader responses.The Journal of experimental medicine · 2025Article
- Finding and filling the knowledge gaps in mechanisms of T cell-mediated TB immunity to inform vaccine design.Nature reviews. Immunology · 2025Review
- Macrophage-T cell interactions promote SLAMF1 expression for enhanced TB defense.Nature communications · 2025Article
- Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.Nature communications · 2025Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- Effect of co-vaccination of cattle with RB51 and BCG on vaccine-specific CD4Frontiers in immunology · 2025Article
- Machine learning of immune-related laboratory indicators enables discrimination between pulmonary and extrapulmonary tuberculosis.Frontiers in medicine · 2025Article
- Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells.Nature communications · 2024Article
- Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.PLoS pathogens · 2024Article
- Heterogeneity in lung macrophage control ofbioRxiv : the preprint server for biology · 2023Article
- Helper T cell bias following tuberculosis chemotherapy identifies opportunities for therapeutic vaccination to prevent relapse.NPJ vaccines · 2023Article
- Article
- Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice.NPJ vaccines · 2023Article
- Recognition and control ofFrontiers in tuberculosis · 2023Review
- Immune evasion and provocation by Mycobacterium tuberculosis.Nature reviews. Microbiology · 2022Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Adaptive immunity to Mycobacterium tuberculosis controls progressive bacterial growth and disease but does not eradicate infection. Among CD4+ T cells in the lungs of M. tuberculosis-infected mice, we observed that few produced IFN-γ without ex vivo restimulation. Therefore, we hypothesized that one mechanism whereby M. tuberculosis avoids elimination is by limiting activation of CD4+ effector T cells at the site of infection in the lungs. To test this hypothesis, we adoptively transferred Th1-polarized CD4+ effector T cells specific for M. tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked to the lungs of infected mice and exhibited antigen-dependent IFN-γ production. During the early phase of infection, ∼10% of P25TCRTh1 cells produced IFN-γ in vivo; this declined to <1% as infection progressed to chronic phase. Bacterial downregulation of fbpB (encoding Ag85B) contributed to the decrease in effector T cell activation in the lungs, as a strain of M. tuberculosis engineered to express fbpB in the chronic phase stimulated P25TCRTh1 effector cells at higher frequencies in vivo, and this resulted in CD4+ T cell-dependent reduction of lung bacterial burdens and prolonged survival of mice. Administration of synthetic peptide 25 alone also increased activation of endogenous antigen-specific effector cells and reduced the bacterial burden in the lungs without apparent host toxicity. These results indicate that CD4+ effector T cells are activated at suboptimal frequencies in tuberculosis, and that increasing effector T cell activation in the lungs by providing one or more epitope peptides may be a successful strategy for TB therapy.
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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.