The extent and magnitude of islet T cell infiltration as powerful tools to define the progression to type 1 diabetes
Authors' conclusion
Our 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.
Study context
- Population
- Organ donors with and without T1D from the Network for Pancreatic Organ Donors with Diabetes; 8661 islets analysed8,661 islets
- Exposure
- Non-diabetic vs double autoantibody-positive vs T1D organ donors
- Non-diabeticn = 15reference
- Autoantibody-positiven = eight
- T1Dn = ten
- Outcome
- Percentage of islets infiltrated by T cells (1-5 CD3+ cells; ≥6 CD3+ cells) and islet T cell density
Methodological detailsorgan donor pancreatic tissue, immunofluorescence
- Organ donor pancreatic tissue
- Immunofluorescence
Main finding
As reported in the abstract
Observational data: associations, not effects.
Further findings
Islets infiltrated by ≥6 CD3+ cells
Islet T cell density
Islets infiltrated by ≥6 CD3+ cells
- CD8+ and CD8- populations followed similar patterns
Islet T cell density
- Significantly higher in autoantibody-positive and T1D vs non-diabetic donors
- Higher exocrine T cell density in T1D
30-30 rule (≥30 islets analysed; reference mean T cell density 30 CD3+ cells/mm²)
- Differentiates non-diabetic and T1D donors with high specificity and sensitivity; classifies autoantibody-positive individuals as non-diabetic or T1D-like
Original publication
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