ArticleBlood2011
Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The trial behind it
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Who cites it
48 citing papers in PubMed, 91 citations in OpenAlex.
- Abatacept treatment shows a modulating effect on Treg subsets in LRBA-deficient patients.Frontiers in immunology · 2026Article
- CD28 and TCR differentially impact naïve and memory T cell responses.Discovery immunology · 2025Article
- Integrative transcriptome analysis reveals the molecular events underlying impaired T-cell responses in EGFR-mutant lung cancer.Scientific reports · 2024Article
- Regulatory T Cells for Control of Autoimmunity.Advances in experimental medicine and biology · 2024Article
- Skin-derived TSLP stimulates skin migratory dendritic cells to promote the expansion of regulatory T cells.European journal of immunology · 2023Article
- IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease.The Journal of clinical investigation · 2022Article
- Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer.Cancer cell · 2022Article
- The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy.Nature communications · 2022Article
- Article
- Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- XBP-1s Promotes B Cell Pathogenicity in Chronic GVHD by Restraining the Activity of Regulated IRE-1α-Dependent Decay.Frontiers in immunology · 2021Article
- Emerging patterns of regulatory T cell function in tuberculosis.Clinical and experimental immunology · 2020Review
- Cutting Edge: Tissue Antigen Expression Levels Fine-Tune T Cell Differentiation Decisions In Vivo.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells.Immune network · 2020Article
- Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Rapamycin and abundant TCR stimulation are required for the generation of stable human induced regulatory T cells.Clinical & translational immunology · 2020Article
- Costimulation Blockade in Vascularized Composite Allotransplantation.Frontiers in immunology · 2020Review
- Rebalancing Immune Homeostasis to Treat Autoimmune Diseases.Trends in immunology · 2019Review
- Mechanisms of human FoxP3Clinical and experimental immunology · 2019Review
- Unregulated antigen-presenting cell activation by T cells breaks self tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
CD28 costimulation is required for the generation of naturally derived regulatory T cells (nTregs) in the thymus through lymphocyte-specific protein tyrosine kinase (Lck) signaling. However, it is not clear how CD28 costimulation regulates the generation of induced Tregs (iTregs) from naive CD4 T-cell precursors in the periphery. To address this question, we induced iTregs (CD25(+)Foxp3(+)) from naive CD4 T cells (CD25(-)Foxp3(-)) by T-cell receptor stimulation with additional transforming growth factorβ (TGFβ) in vitro, and found that the generation of iTregs was inversely related to the level of CD28 costimulation independently of IL-2. Using a series of transgenic mice on a CD28-deficient background that bears wild-type or mutated CD28 in its cytosolic tail that is incapable of binding to Lck, phosphoinositide 3-kinase (PI3K), or IL-2-inducible T-cell kinase (Itk), we found that CD28-mediated Lck signaling plays an essential role in the suppression of iTreg generation under strong CD28 costimulation. Furthermore, we demonstrate that T cells with the CD28 receptor incapable of activating Lck were prone to iTreg induction in vivo, which contributed to their reduced ability to cause graft-versus-host disease. These findings reveal a novel mechanistic insight into how CD28 costimulation negatively regulates the generation of iTregs, and provide a rationale for promoting T-cell immunity or tolerance by regulating Tregs through targeting CD28 signaling.
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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.