ArticleThe Journal of clinical investigation2001
Signaling through CD28 and CTLA-4 controls two distinct forms of T cell anergy.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis.World journal of gastroenterology · 2015Pooled it
- Targeting the pMHC-TCR Interaction: Molecular Strategies and Therapeutic Potential in Autoimmunity.International journal of molecular sciences · 2026Review
- T cell exhaustion in parasitic infections.Frontiers in immunology · 2026Review
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- RORγt+Foxp3+ regulatory T cells in the regulation of autoimmune arthritis.Clinical and experimental immunology · 2022Article
- Continuous Modeling of T CD4 Lymphocyte Activation and Function.Frontiers in immunology · 2021Article
- Conversion of Anergic T Cells Into Foxp3Frontiers in immunology · 2021Article
- Functional crosstalk between T cells and monocytes in cancer and atherosclerosis.Journal of leukocyte biology · 2020Review
- Tumor microenvironmental influences on dendritic cell and T cell function: A focus on clinically relevant immunologic and metabolic checkpoints.Clinical and translational medicine · 2020Review
- The Integrative Analysis Identifies Three Cancer Subtypes and Stemness Features in Cutaneous Melanoma.Frontiers in molecular biosciences · 2020Article
- BTLA Expression on Th1, Th2 and Th17 Effector T-Cells of Patients with Systemic Lupus Erythematosus Is Associated with Active Disease.International journal of molecular sciences · 2019Article
- Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance.Scientific reports · 2019Article
- Article
- Distribution of Cytotoxic T Lymphocyte-Associated Antigen-4 Promoter Polymorphisms in Taiwanese Patients with Type 2 Diabetes Mellitus.International journal of medical sciences · 2018Article
- Article
- ATVB Distinguished Scientist Award: How Costimulatory and Coinhibitory Pathways Shape Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2017Review
- Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches.Cellular & molecular immunology · 2017Review
- Impact of Metabolism on T-Cell Differentiation and Function and Cross Talk with Tumor Microenvironment.Frontiers in immunology · 2017Review
- Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Induction of CD4(+) Regulatory and Polarized Effector/helper T Cells by Dendritic Cells.Immune network · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Primary T cell proliferative responses to TCR ligation plus CD28 costimulation are surprisingly heterogeneous. Many cells that enter G1 fail to progress further through the cell cycle, and some of these cells subsequently fail to divide upon restimulation, even in the presence of IL-2. Such IL-2-refractory anergy is distinct from the IL-2-reversible anergy induced by TCR occupancy in the absence of CD28 costimulation. Here, we focus on the contributions of cell cycle progression and costimulatory (CD28/CTLA-4) signals in the regulation of anergy. We show that CD28 costimulation is not sufficient for anergy avoidance and that activated T cells must progress through the cell cycle in order to escape anergy. Induction of this "division-arrest" form of anergy requires CTLA-4 signaling during the primary response. Also, cell division per se is not sufficient for anergy avoidance: the few T cells that undergo multiple rounds of cell division during overt CD28 costimulatory blockade do not escape the ultimate induction of clonal anergy. Anergy avoidance by primary T cells is thus a multistep process: in order to participate in a productive immune response, an individual T cell activated through its antigen receptor must receive CD28 costimulation and progress through the cell cycle. Anergy may be induced either through a combination of CTLA-4 signaling and the failure of cell cycle progression, or through a proliferation-independent mechanism in which TCR ligation occurs in the absence of CD28.
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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.