ArticleJCI insight2018
Selective CD28 blockade attenuates CTLA-4-dependent CD8+ memory T cell effector function and prolongs graft survival.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Trial
- Blinatumomab bypasses CD28 blockade to sustain T-cell cytotoxicity and improve survival in a xenograft B-ALL model.Journal for immunotherapy of cancer · 2026Article
- Identification of key genes related to arginine metabolism in immunoglobulin A nephropathy through the combination of scRNA-seq and bulk RNA-seq data.Frontiers in immunology · 2026Article
- CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.Bioorganic & medicinal chemistry letters · 2025Review
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- The impact of different immunosuppressants and acute immune rejection on clinical outcomes in diverse solid organ transplant recipients.Frontiers in immunology · 2025Article
- Fine-tuning tumor- and allo-immunity: advances in the use of immune checkpoint inhibitors in kidney transplant recipients.Clinical kidney journal · 2024Review
- Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?Journal of personalized medicine · 2024Review
- Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future.Kidney international reports · 2023Review
- Nanobodies; new molecular instruments with special specifications for targeting, diagnosis and treatment of triple-negative breast cancer.Cancer cell international · 2022Review
- Linked sensitization by memory CD4+ T cells prevents costimulation blockade-induced transplantation tolerance.JCI insight · 2022Article
- Control of Memory Phenotype T Lymphocyte Homeostasis: Role of Costimulation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Selective CD28 blockade impacts T cell differentiation during homeostatic reconstitution following lymphodepletion.Frontiers in immunology · 2022Article
- A Nanobody Against Cytotoxic T-Lymphocyte Associated Antigen-4 Increases the Anti-Tumor Effects of Specific CD8Journal of biomedical nanotechnology · 2019Article
- T cell checkpoint regulators in the heart.Cardiovascular research · 2019Review
- 2B4 Mediates Inhibition of CD8Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Influence of T Cell Coinhibitory Molecules on CD8Frontiers in immunology · 2018Review
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
Abstract
Memory T cells pose a significant problem to successful therapeutic control of unwanted immune responses during autoimmunity and transplantation, as they are differentially controlled by cosignaling receptors such as CD28 and CTLA-4. Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80 and CD86, but they also have the unintended consequence of blocking the ligands for CTLA-4, a process that may inadvertently boost effector responses. Here, we show that a potentially novel anti-CD28 domain antibody (dAb) that selectively blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival in sensitized recipients as compared with CTLA-4 Ig. However, both CTLA-4 Ig and anti-CD28 dAb similarly and significantly reduced the accumulation of donor-reactive CD8+ memory T cells, demonstrating that regulation of the expansion of CD8+ memory T cell populations is controlled in part by CD28 signals and is not significantly impacted by CTLA-4. In contrast, selective CD28 blockade was superior to CTLA-4 Ig in inhibiting IFN-γ, TNF, and IL-2 production by CD8+ memory T cells, which in turn resulted in reduced recruitment of innate CD11b+ monocytes into allografts. Importantly, this superiority was CTLA-4 dependent, demonstrating that effector function of CD8+ memory T cells is regulated by the balance of CD28 and CTLA-4 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.