Abstract

Type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of β-cells, but the immunological basis for T1D remains controversial. Microbial diversity promotes the maturation and activation of certain immune subsets, including CD161bright CD8+ mucosal associated invariant T (MAIT) cells, and alterations in gut mucosal responses have been reported in type 1 diabetics (T1Ds). We analyzed T cell populations in peripheral blood leukocytes from juvenile T1Ds and healthy controls. We found that proportion and absolute number of MAIT cells were similar between T1Ds and controls. Furthermore, while MAIT cell proportions increased with age among healthy controls, this trend was not observed among long-standing T1Ds. Additionally, the CD27- MAIT cell subset is significantly increased in T1Ds and positively correlated with HbA1c levels. However, after T1Ds are stratified by age, the younger group has significantly increased proportions of CD27- MAIT cells compared to age-matched controls, and this proportional increase appears to be independent of HbA1c levels. Finally, we analyzed function of the CD27- MAIT cells and observed that IL-17A production is increased in CD27- compared to CD27+ MAIT cells. Overall, our data reveal disparate MAIT cell dynamics between T1Ds and controls, as well as signs of increased MAIT cell activation in T1Ds. These changes may be linked to hyperglycemia and increased mucosal challenge among T1Ds.

Highlights

  • Human type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of insulin-producing β cells within the pancreatic islets

  • The proportion of CD27- mucosal associated invariant T (MAIT) cells is significantly increased in juvenile type 1 diabetics

  • We reasoned that if T1Ds suffered from altered intestinal immunity, we may observe altered proportions and absolute numbers of MAIT cells

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Summary

Introduction

Human type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of insulin-producing β cells within the pancreatic islets. While genome-wide association studies have implicated several immune-related factors with the risk of clinical disease [8, 9], such factors are predictive in only a minority of patients [10, 11]. From these results and multiple epidemiological studies [12], it is widely accepted that environmental stimuli play a fundamental role in disease onset, and that the face of disease observed in the clinic may represent heterogeneous ontologies

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