ArticleScandinavian journal of immunology2014
Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics.
Article in Scandinavian journal of immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Differential Expression of Cytotoxic-Associated Markers in Circulating CD4International journal of molecular sciences · 2026Article
- Epigenetic Alterations in Microbiome-Host Interactions in Inflammatory and Autoimmune Diseases.International journal of molecular sciences · 2026Review
- Review
- Osteoimmunology: Crosstalk Between T Cells and Osteoclasts in Osteoporosis.Clinical reviews in allergy & immunology · 2025Review
- An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.Science China. Life sciences · 2025Review
- Are immunosenescent T cells really senescent?Aging cell · 2024Review
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- New Targets and Strategies for Rheumatoid Arthritis: From Signal Transduction to Epigenetic Aspect.Biomolecules · 2023Review
- Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern in the Osteoimmunology Arena.Aging and disease · 2021Article
- Acquisition of New Migratory Properties by Highly Differentiated CD4+CD28Journal of personalized medicine · 2021Article
- Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases.Frontiers in immunology · 2021Review
- Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis.Frontiers in neurology · 2021Review
- Article
- Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.Journal of clinical laboratory analysis · 2020Article
- Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4Frontiers in immunology · 2020Article
- Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression.Immunity & ageing : I & A · 2020Review
- Epigenetic Regulation in the Pathogenesis of Sjögren Syndrome and Rheumatoid Arthritis.Frontiers in genetics · 2019Review
- Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges.British journal of pharmacology · 2017Review
- Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis.Nature genetics · 2017Article
- Asthma and the Risk of Rheumatoid Arthritis: An Insight into the Heterogeneity and Phenotypes of Asthma.Tuberculosis and respiratory diseases · 2017Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population.
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Registered trials
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