ArticlePLoS pathogens2016
CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 1 of them a synthesis that pooled it.
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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
224 citing papers in PubMed, 1 synthesis or guideline pooled it, 337 citations in OpenAlex.
- Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development.Frontiers in immunology · 2022Pooled it
- Exacerbation of CMV and Nontuberculous Mycobacterial Infections Following PD-1 Blockade for HIV-Associated Kaposi Sarcoma.Open forum infectious diseases · 2024Trial
- Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum.The Journal of infectious diseases · 2022Trial
- Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung.The Journal of clinical investigation · 2021Trial
- Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines.Communications biology · 2020Trial
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Single-cell transcriptomics reveal PD-1-loss-driven immune dysregulation of pulmonary lymphocytes during earlyMicrobiology spectrum · 2026Article
- Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts.Nature immunology · 2026Article
- The study of immunological markers in tuberculosis across animal models and its translation to human research.Lab animal · 2026Review
- Impaired IFNγ responsiveness of monocyte-derived lung cells limits immunity to Mycobacterium tuberculosis.Nature communications · 2026Article
- Diverse infection models demonstrate robust resistance ofbioRxiv : the preprint server for biology · 2026Article
- Immune endotypes in tuberculosis: Keys to decoding disease complexity.Journal of internal medicine · 2026Review
- HowVaccines · 2026Review
- IFNγ blockade in Mycobacterium tuberculosis infected macaques alters the granuloma environment but not bacterial control.Nature communications · 2026Article
- Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Immunotherapy for Melanoma in Patients with Altered Immune Systems: Unique Challenges and Clinical Considerations.Advances in therapy · 2026Review
- Strong sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- AFrontiers in tuberculosis · 2026Article
- Enhancing tuberculosis vaccine efficacy with a heterologous mRNA-ChAdOx1 prime-pull strategy targeting lung-resident memory T cells.Frontiers in immunology · 2026Article
- Lung squamous cell carcinoma complicated with immune checkpoint inhibitor-associated active tuberculosis: a case report and literature review.Frontiers in oncology · 2026Article
164 more citing papers are in PubMed but not listed here.
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 5 institutions in 1 country.
Funding
Abstract
IFN-γ-producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here we show that IFN-γ accounts for only ~30% of CD4 T cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen. Moreover, increasing the IFN-γ-producing capacity of CD4 T cells by ~2 fold exacerbates lung infection and leads to the early death of the host, despite enhancing control in the spleen. In addition, we show that the inhibitory receptor PD-1 facilitates host resistance to Mtb by preventing the detrimental over-production of IFN-γ by CD4 T cells. Specifically, PD-1 suppressed the parenchymal accumulation of and pathogenic IFN-γ production by the CXCR3+KLRG1-CX3CR1- subset of lung-homing CD4 T cells that otherwise mediates control of Mtb infection. Therefore, the primary role for T cell-derived IFN-γ in Mtb infection is at extra-pulmonary sites, and the host-protective subset of CD4 T cells requires negative regulation of IFN-γ production by PD-1 to prevent lethal immune-mediated pathology.
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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.