Evaluating T cell responses prior to the onset of type 1 diabetes

Sefina Arif*, Norkhairin Yusuf, Clara Domingo-Vila, Yuk Fun Liu, Polly J. Bingley, Mark Peakman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Aims: In the current study we aimed to evaluat T cell phenotypes and metabolic profiles in high-risk individuals who progressed to type 1 diabetes compared to those remaining disease free. Methods: A Fluorspot assay was used to examine T cell responses to a panel of islet autoantigen peptides in samples obtained 6- and 30-months preceding disease onset and at the same timepoints in non-progressors. Results: We noted a significant increase in the magnitude of the proinflammatory interferon-γ response to proinsulin and insulin peptides in individuals who progressed to type 1 diabetes. In contrast, in the non-progressors, we observed an increase in the regulatory IL-10 response to proinsulin peptides. Furthermore, the T cell responses to the islet peptide panel predisposed towards a proinflammatory interferon-γ bias in the progressors. Conclusions: Collectively, these data suggest that a proinflammatory T cell response is prevalent in high-risk individuals who progress to type 1 diabetes and can be detected up to 6 months prior to onset of disease. This observation, albeit in a small cohort, can potentially be harnessed in disease staging, particularly in identifying autoantibody-positive individuals transitioning from stage 2 (dysglycemia present and pre-symptomatic) to stage 3 (dysglycemia present and symptomatic). The detection of these different T cell phenotypes in progressors and non-progressors suggests the presence of disease endotypes.

Original languageEnglish
Article numbere14860
JournalDiabetic Medicine
Volume39
Issue number9
DOIs
Publication statusPublished - Sept 2022

Keywords

  • antibody
  • cytokines
  • interferon-γ
  • proinsulin
  • T cells
  • type 1 diabetes

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