Trial reportPLoS pathogens2012
Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions.
Trial report in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.Frontiers in immunology · 2021Pooled it
- A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates.Cancer immunology, immunotherapy : CII · 2014Trial
- T cell-macrophage interactions in tuberculosis: What we've got here is failure to communicate.Journal of internal medicine · 2026Review
- CD226 identifies effector CD8Cell reports · 2025Article
- Article
- TIGIT blockade improves anti-Mycobacterium tuberculosis immunity.PLoS pathogens · 2025Article
- The role of Tim-3+T cell subsets in the peripheral blood of patients with COVID-19 and diabetes.iScience · 2025Article
- Macrophage miR-4524a-5p/TBP promotes β-TrCP -TIM3 complex activation and TGFβ release and aggravates NAFLD-associated fibrosis.Cell death & disease · 2025Article
- Regulatory Mechanisms of Co-Inhibitory Receptors in Tuberculosis Immunity: Implications for Therapeutic Targets.ImmunoTargets and therapy · 2025Review
- Reprogramming the host: Mycobacterium tuberculosis as a silent architect of the immuno-tumoral.Frontiers in cellular and infection microbiology · 2025Review
- TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3.Communications biology · 2024Article
- Tim-3 Is Not Required for Establishment of CD8+ T Cell Memory to Lymphocytic Choriomeningitis Virus.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Association of tuberculosis risk with genetic polymorphisms of the immune checkpoint genes PDCD1, CTLA-4, and TIM3.PloS one · 2024Article
- Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.Frontiers in immunology · 2023Article
- Characterization of CD4Frontiers in immunology · 2023Article
- The paradox of immune checkpoint inhibition re-activating tuberculosis.The European respiratory journal · 2022Review
- Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy.Biomarker research · 2022Review
- Immunomodulatory Properties of Immune Checkpoint Inhibitors-More than Boosting T-Cell Responses?Cancers · 2022Review
- CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis.Microbiology spectrum · 2022Article
- T cell immunoglobulin and mucin domain-containing protein 3 is highly expressed in patients with acute decompensated heart failure and predicts mid-term prognosis.Frontiers in cardiovascular medicine · 2022Article
7 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
18 authors at 8 institutions in 2 countries.
Funding
Abstract
T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. Mechanistic experiments showed that siRNA silencing of Tim-3 or soluble Tim-3 treatment interfering with membrane Tim-3-ligand interaction reduced de novo production of IFN-γ and TNF-α by Tim-3-expressing T cells. Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. This study therefore uncovered a previously unknown mechanism for T-cell immune responses regulated by Tim-3, and findings may have implications for potential immune intervention in TB.
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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.