ArticleDiabetologia2023
The extent and magnitude of islet T cell infiltration as powerful tools to define the progression to type 1 diabetes.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Clinical parameters and emerging biomarkers of partial remission in pediatric type 1 diabetes: a systematic review.Frontiers in endocrinology · 2026Pooled it
- Deep learning-powered quantification of endocrine cells and CD3Diabetologia · 2026Article
- Beta cell-targeted PD-1 agonist inhibits cell-mediated autoimmunity in pancreas tissue slices.Science advances · 2026Article
- Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression.Nature communications · 2026Article
- Revisiting type 1 diabetes progression in the non-obese diabetic mouse.Scientific reports · 2026Article
- Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production.Frontiers in immunology · 2026Article
- Small things matter: Lack of extraislet β cells in type 1 diabetes.Science advances · 2025Article
- Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices.bioRxiv : the preprint server for biology · 2025Article
- Post-Translational Modified Neoantigens in Autoimmune Diseases: Challenges of Immune Tolerance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians.Diabetes, obesity & metabolism · 2025Review
- Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression.bioRxiv : the preprint server for biology · 2025Article
- Tissue Resident and Infiltrating Immune Cells: Their Influence on the Demise of Beta Cells in Type 1 Diabetes.Biomolecules · 2025Review
- Leveraging pre-trained machine learning models for islet quantification in type 1 diabetes.Journal of pathology informatics · 2025Article
- Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.Biomedicines · 2024Article
- Insights in Nutrition to Optimize Type 1 Diabetes Therapy.Nutrients · 2024Review
- A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes.Cell reports. Medicine · 2024Article
- Cross-sectional imaging of the pancreas in diabetes.Abdominal radiology (New York) · 2024Review
- Insulitis in human type 1 diabetes: lessons from an enigmatic lesion.European journal of endocrinology · 2024Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas.Cell metabolism · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulitis is not present in all islets, and it is elusive in humans. Although earlier studies focused on islets that fulfilled certain criteria (e.g. ≥15 CD45
methodsPancreatic tissue sections from 15 non-diabetic, eight double autoantibody-positive and ten type 1 diabetic (0-2 years of disease duration) organ donors were obtained from the Network for Pancreatic Organ Donors with Diabetes, and stained for insulin, glucagon, CD3 and CD8 by immunofluorescence. T cell infiltration was quantified in a total of 8661 islets using the software QuPath. The percentage of infiltrated islets and islet T cell density were calculated. To help standardise the analysis of T cell infiltration, we used cell density data to develop a new T cell density threshold capable of differentiating non-diabetic and type 1 diabetic donors.
resultsOur analysis revealed that 17.1% of islets in non-diabetic donors, 33% of islets in autoantibody-positive and 32.5% of islets in type 1 diabetic donors were infiltrated by 1 to 5 CD3 CONCLUSIONS/
interpretationOur data indicates that the proportion of infiltrated islets and T cell density change dramatically during the course of type 1 diabetes, and these changes can be already observed in double autoantibody-positive individuals. This suggests that, as disease progresses, T cell infiltration extends throughout the pancreas, reaching the islets and exocrine compartment. While it predominantly targets insulin-containing islets, large accumulations of cells are rare. Our study fulfils the need to further understand T cell infiltration, not only after diagnosis but also in individuals with diabetes-related autoantibodies. Furthermore, the development and application of new analytical tools based on T cell infiltration, like the 30-30 rule, will allow us to correlate islet infiltration with demographic and clinical variables with the aim of identifying individuals at the very early stages of the disease.
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