ReviewImmunoTargets and therapy2015
CD28 co-stimulation in T-cell homeostasis: a recent perspective.
Review in ImmunoTargets and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.
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Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Global research prospects and trends in TFH cells and tumors: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Yoga maintains Th17/Treg cell homeostasis and reduces the rate of T cell aging in rheumatoid arthritis: a randomized controlled trial.Scientific reports · 2023Trial
- CTLA-4: a promising immunosuppressive immune checkpoint in prostate cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Studying Macromolecular Composition in Cell-Cell Interfaces Using 3D Membrane Reconstitution Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- A nine-gene nicotine-metabolism signature predicts prognosis and characterizes the immune landscape in colon adenocarcinoma.Journal of gastrointestinal oncology · 2026Article
- The insider's perspective: The intracellular complosome and immune cell dynamics in cancer.Clinical and translational medicine · 2026Review
- Viral infections in solid organ transplant recipients: immunological principles and intervention strategies.American journal of translational research · 2026Review
- A dual compartment peripheral blood signature of soluble and membrane-bound immune checkpoints predicts outcome in lymphoma patients.Oncoimmunology · 2025Article
- Review
- Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.Immunotherapy · 2025Review
- Mitigation strategies for gastrointestinal (GI) immune-related adverse events for patients with solid tumors receiving immunotherapy.Immunotherapy · 2025Review
- The Importance of Particle Shape: Effect of Nonspherical Particles and Their Stabilized Pickering Emulsions on Immunization Efficacy.Small science · 2025Article
- Non-coding RNAs as potential mediators of resistance to lung cancer immunotherapy and chemotherapy.Oncology research · 2025Review
- Computational insights in CD58 binding to ASFV CD2v and in silico optimization of nanobody designs against the interface.Open veterinary journal · 2025Article
- The role of actin cytoskeleton component Arp2/3 in inflammatory response.Frontiers in cell and developmental biology · 2025Review
- Association between immune cells and membranous nephropathy: a two-sample Mendelian randomization study.Archives of medical science : AMS · 2025Article
- Regulation of actin cytoskeletal dynamics in T cell development and function.Frontiers in immunology · 2025Review
38 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cells play a key role within the adaptive immune system mediating cellular immunity and orchestrating the immune response as a whole. Their activation requires not only recognition of antigen/major histocompatibility complexes by the T-cell receptor but in addition co-stimulation via the CD28 molecule through binding to CD80, CD86, or as recently discovered, inducible co-stimulator ligand expressed by antigen-presenting cells. Apart from tight control of the co-stimulatory signal by the T-cell receptor complex, expression of the inhibitory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) sharing its ligands with CD28 is required to avoid inappropriate or prolonged T-cell activation. CD4(+) Foxp3(+) regulatory T (Treg) cells, which are crucial inhibitors of autoimmunity, add another level of complexity in that they differ from conventional non-regulatory CD4(+) T-cells by strongly depending on CD28 signaling for their generation and homeostasis. Moreover, CTLA-4 is constitutively expressed by Treg cells where it serves as a key mediator of suppression, while conventional CD4(+) T-cells express CTLA-4 only after activation. Here, we discuss recent insights into the molecular events underlying CD28-mediated co-stimulation, its impact on gene regulation, and the differential role of CD28 expression on Treg cells versus conventional CD4(+) and CD8(+) T-cells. Moreover, we summarize the exciting therapeutic options which have arisen from our current understanding of T-cell co-stimulation. Some of these have already been translated into the clinic, while others are expected to follow soon due to promising preclinical results. In particular, we discuss the failed 2006 trial of the CD28 superagonist TGN1412, and the return of this potent T-cell activator to clinical development.
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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.