ArticleThe Journal of clinical investigation2012
Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses 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
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.Frontiers in immunology · 2021Pooled it
- Pharmacokinetics, lineage identity, and trafficking of ex vivo expanded polyclonal regulatory T cells in a prospective randomized clinical trial of kidney transplant recipients with allograft inflammation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Trial
- Memory Regulatory T cells Increase Only In Inflammatory Phase of Chronic Hepatitis B Infection and Related to Galectin-9/Tim-3 interaction.Scientific reports · 2017Trial
- Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.European journal of immunology · 2014Trial
- Article
- Prognostic Impact and Clinicopathological Significance of TIM-3 and LAG-3 Expressions in Laryngeal Squamous Cell Carcinoma.Laryngoscope investigative otolaryngology · 2026Article
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Expression of TIM-3 and Gal-9 Immune Checkpoints in Chronic Lymphocytic Leukemia: The Potential Role of Interleukin-27.Current issues in molecular biology · 2025Article
- The homeostasis and heterogeneity of regulatory T cells in sepsis.Burns & trauma · 2025Article
- Tim-3 Is Required for Regulatory T Cell-Mediated Promotion of T Cell Exhaustion and Viral Persistence during Chronic Lymphocytic Choriomeningitis Virus Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Review
- TIM proteins and microRNAs: distinct impact and promising interactions on transplantation immunity.Frontiers in immunology · 2024Review
- Immune Checkpoints in Solid Organ Transplantation.Biology · 2023Review
- Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer.Journal of translational medicine · 2023Article
- TIM-3 signaling contributes to the suppressive capacity of Tregs from people with HIV on antiretroviral therapy.Journal of leukocyte biology · 2023Article
- Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immune Checkpoints and targeted agents in relapse and graft-versus-host disease after hematopoietic stem cell transplantation.Molecular biology reports · 2023Review
- Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment.Molecular cancer · 2023Review
15 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 1 institution in 1 country.
Funding
Abstract
Tregs play a pivotal role in inducing and maintaining donor-specific transplant tolerance. The T cell immunoglobulin and mucin domain-3 protein (TIM-3) is expressed on many fully activated effector T cells. Along with program death 1 (PD-1), TIM-3 is used as a marker for exhausted effector T cells, and interaction with its ligand, galectin-9, leads to selective death of TIM-3+ cells. We report herein the presence of a galectin-9-sensitive CD4+FoxP3+TIM-3+ population of T cells, which arose from CD4+FoxP3+TIM-3- proliferating T cells in vitro and in vivo and were often PD-1+. These cells became very prominent among graft-infiltrating Tregs during allograft response. The frequency and number of TIM-3+ Tregs peaked at the time of graft rejection and declined thereafter. Moreover, these cells also arise in a tolerance-promoting donor-specific transfusion model, representing a pool of proliferating, donor-specific Tregs. Compared with TIM-3- Tregs, TIM-3+ Tregs, which are often PD-1+ as well, exhibited higher in vitro effector function and more robust expression of CD25, CD39, CD73, CTLA-4, IL-10, and TGF-β but not galectin-9. However, these TIM-3+ Tregs did not flourish when passively transferred to newly transplanted hosts. These data suggest that a heretofore unrecognized graft-infiltrating, short-lived subset of Tregs can restrain rejection.
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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.