ArticleFrontiers in immunology2016
Differential Expression of Immune Checkpoint Modulators on In Vitro Primed CD4(+) and CD8(+) T Cells.
Article in Frontiers in immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Upregulation of cellular exhaustion-related genes and CD4 + T cell disturbances in immunological non-responders on antiretroviral therapy.Immunologic research · 2026Article
- A Predictive Immunological Signature Associated with Pathological Response in Breast Cancer Treated with Neoadjuvant Chemotherapy.Biomedicines · 2026Article
- Integrated multi-omics reveals the ITGB2-IL2RB-NK axis in promoting papillary thyroid carcinoma progression and immune microenvironment crosstalk.Discover oncology · 2026Article
- Crosstalk between innate immune signaling pathways and integrated TLR, NLRP3 inflammasome, cGAS-STING, and NF-κB networks in sepsis.Frontiers in cell and developmental biology · 2026Review
- Immune Checkpoint Restoration as a Therapeutic Strategy to Halt Diabetes-Driven Atherosclerosis.Biology · 2025Review
- Transient EZH2 Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell Stemness and Improves Adoptive T-Cell Therapy.Cancer immunology research · 2025Article
- Characterization of CD4Frontiers in immunology · 2023Article
- Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.Frontiers in immunology · 2023Article
- Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression.JCI insight · 2022Article
- The immune landscape of common CNS malignancies: implications for immunotherapy.Nature reviews. Clinical oncology · 2021Review
- Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Quantitative and functional characteristics of circulating and bone marrow PD-1- and TIM-3-positive T cells in treated multiple myeloma patients.Scientific reports · 2020Article
- Effect of age and sex on immune checkpoint expression and kinetics in human T cells.Immunity & ageing : I & A · 2020Article
- Radiation with STAT3 Blockade Triggers Dendritic Cell-T cell Interactions in the Glioma Microenvironment and Therapeutic Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Are radiation and response biomarkers the missing elements for efficacious immunotherapy for glioma patients?Neuro-oncology · 2020Article
- Syngeneic Mesenchymal Stem Cells Reduce Immune Rejection After Induced Pluripotent Stem Cell-Derived Allogeneic Cardiomyocyte Transplantation.Scientific reports · 2020Article
- Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer.Disease markers · 2019Article
- Metabolic pathway activation distinguishes transcriptional signatures of CD8+ T cells from HIV-1 elite controllers.AIDS (London, England) · 2018Article
- TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Sorafenib combined with HER-2 targeted vaccination can promote effective T cell immunity in vivo.International immunopharmacology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PD-1, TIM-3, and LAG-3 are molecules shown to have immune modulatory properties, and although initially classified as indicators of T cell hyporesponsiveness, it has become clear that they are also associated with the normal course of T cell activation. Functional studies have focused mainly on CD8(+) T cells during chronic inflammation due to interest in co-opting the cellular immune response to eliminate viral or cancerous threats; however, there remains a relative lack of data regarding the expression of these molecules on CD4(+) T cells. Here, we report that expression of the immune checkpoint (IC) molecules PD-1, LAG-3, and TIM-3 are differentially expressed on CD4(+) and CD8(+) T cells in the allogeneic response resulting from a mixed lymphocyte reaction. In these studies, PD-1 expression is higher on CD4(+) T cells compared to CD8(+) T cells. In contrast, TIM-3 is expressed at higher levels on CD8(+) T cells compared to CD4(+) T cells with an apparent reciprocity in that PD-1(+) CD4(+) T cells are frequently TIM-3(lo/-), while TIM-3-expressing CD8(+) T cells are largely PD-1(lo/-). In addition, there is a decrease in the frequency of TIM-3(+) CD4(+) cells producing IFN-γ and IL-5 compared to TIM-3(+) CD8(+) cells. Lastly, the memory T cell phenotype within each IC-expressing subset differs between CD4(+) and CD8(+) T cells. These findings highlight key differences in IC expression patterns between CD4(+) and CD8(+) T cells and may allow for more effective therapeutic targeting of these molecules in the future.
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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.