Trial reportThe Journal of clinical investigation2020
Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
106 citing papers in PubMed, 3 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Vascular endothelial growth factor as a potential biomarker in systemic sclerosis: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Circulating cell adhesion molecules in systemic sclerosis: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Lactobacillus plantarum-derived indole-3-lactic acid inhibits prostate cancer progression through ASF1B/ENO1 axis and remodels the tumor microenvironment to enhance anti-PD-1 therapy.Molecular biomedicine · 2026Article
- Development and internal validation of an interpretable machine learning model using routine laboratory data for systemic sclerosis-associated pulmonary arterial hypertension.Rheumatology international · 2026Article
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- A CD57+CD8+ T cell subset links T cell cytotoxicity to fibrotic lung disease in systemic sclerosis.The Journal of clinical investigation · 2026Article
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Macrophages Are Critical Inducers of Bleomycin-Induced Fibrosis in a Systemic Scleroderma Model.The American journal of pathology · 2026Article
- CAR-T cells in systemic sclerosis.Clinical rheumatology · 2026Review
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Dermatomyositis and antisynthetase syndrome disease activity is associated with the expansion of peripheral GZMBFrontiers in immunology · 2026Article
- Quercetin attenuates skin inflammation and fibrosis in systemic sclerosis by targeting the RELA/c-Jun axis to suppress th17 cell responses.Frontiers in immunology · 2026Article
- Analysis of the Correlation between Prognostic Nutritional Index and Diabetic Retinopathy in Patients with Diabetes.Endocrine, metabolic & immune disorders drug targets · 2026Article
- CD8+ T cells drive myofibroblast activation and contraction via JAK/STAT3 and TGFβ signaling.iScience · 2025Article
- Transcriptome analysis unveils Th1 cell cycle signature as a distinctive feature of mixed connective tissue disease.Arthritis research & therapy · 2025Article
- Systemic sclerosis: pathogenic mechanisms and their implications for treatment.Seminars in immunopathology · 2025Review
- Decoding vascular dysfunction in systemic sclerosis: from endothelial damage to clinical implications.Current opinion in rheumatology · 2025Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR-expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4+ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.
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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.