Type 1 diabetes

The extent and magnitude of islet T cell infiltration as powerful tools to define the progression to type 1 diabetes

DiabetologiaPublished Cross-sectional study

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

Islets infiltrated by 1 to 5 CD3+ cells

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

The extent and magnitude of islet T cell infiltration as powerful tools to define the progression to type 1 diabetes. Diabetologia. Published 8 March 2023. doi:10.1007/s00125-023-05888-6

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