ArticleJCI insight2023
Responders to low-dose ATG induce CD4+ T cell exhaustion in type 1 diabetes.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02215200 (Antithymocyte Globulin), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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.
Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Therapeutic potential of anti-thymocyte globulin in type 1 diabetes: A systematic review.PloS one · 2025Pooled it
- Serum exocrine pancreas enzymes are biomarkers of immunotherapy response in new-onset type 1 diabetes.Frontiers in endocrinology · 2024Trial
- Immune dysregulation and stem-like CD8+ T cell enrichment in type 1 diabetes pancreatic lymph nodes.The Journal of clinical investigation · 2026Article
- Low-Dose Antithymocyte Globulin in Type 1 Diabetes: Real-World Exploratory Observation of C-Peptide by Modified Quantitative Response (mQR).Diabetes care · 2026Article
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Aberrant immune regulation and enrichment of stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4Frontiers in immunology · 2026Article
- Regulatory T cell therapy in autoimmune and immune-mediated diseases: from basic research to clinical practice and future perspectives.Frontiers in immunology · 2026Review
- Artificial intelligence-driven therapeutics for disease modification in type 1 diabetes: a digital public health and clinical translation framework.Frontiers in public health · 2026Review
- The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetes care · 2025Review
- Review
- Article
- The heterogeneity of type 1 diabetes: implications for pathogenesis, prevention, and treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2025Review
- Type 1 Diabetes TrialNet: Leading the Charge in Disease Prediction, Prevention, and Immunotherapeutic Mechanistic Understanding.Diabetes care · 2025Review
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- A donor PD-1Signal transduction and targeted therapy · 2025Article
- T Cell Exhaustion in Allergic Diseases and Allergen Immunotherapy: A Novel Biomarker?Current allergy and asthma reports · 2025Review
- Leveraging artificial intelligence and machine learning to accelerate discovery of disease-modifying therapies in type 1 diabetes.Diabetologia · 2025Review
- Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.Hormone research in paediatrics · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUNDLow-dose anti-thymocyte globulin (ATG) transiently preserves C-peptide and lowers HbA1c in individuals with recent-onset type 1 diabetes (T1D); however, the mechanisms of action and features of the response remain unclear. Here, we characterized the post hoc immunological outcomes of ATG administration and their potential use as biomarkers of metabolic response to therapy (i.e., improved preservation of endogenous insulin production).METHODSWe assessed gene and protein expression, targeted gene methylation, and cytokine concentrations in peripheral blood following treatment with ATG (n = 29), ATG plus granulocyte colony-stimulating factor (ATG/G-CSF, n = 28), or placebo (n = 31).RESULTSTreatment with low-dose ATG preserved regulatory T cells (Tregs), as measured by stable methylation of FOXP3 Treg-specific demethylation region (TSDR) and increased proportions of CD4+FOXP3+ Tregs (P < 0.001) identified by flow cytometry. While treatment effects were consistent across participants, not all maintained C-peptide. Responders exhibited a transient rise in IL-6, IP-10, and TNF-α (P < 0.05 for all) 2 weeks after treatment and a durable CD4+ exhaustion phenotype (increased PD-1+KLRG1+CD57- on CD4+ T cells [P = 0.011] and PD1+CD4+ Temra MFI [P < 0.001] at 12 weeks, following ATG and ATG/G-CSF, respectively). ATG nonresponders displayed higher proportions of senescent T cells (at baseline and after treatment) and increased methylation of EOMES (i.e., less expression of this exhaustion marker).CONCLUSIONAltogether in these exploratory analyses, Th1 inflammation-associated serum and CD4+ exhaustion transcript and cellular phenotyping profiles may be useful for identifying signatures of clinical response to ATG in T1D.TRIAL REGISTRATIONClinicalTrials.gov NCT02215200.FUNDINGThe Leona M. and Harry B. Helmsley Charitable Trust (2019PG-T1D011), the NIH (R01 DK106191 Supplement, K08 DK128628), NIH TrialNet (U01 DK085461), and the NIH NIAID (P01 AI042288).
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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.