Altered MAIT phenotype in children with newly diagnosed type 1 diabetes but not in autoantibody-positive at-risk children

Background: Mucosal associated invariant T (MAIT) cells are unconventional T cells, enriched in gut. They express an invariant T-cell receptor and recognize riboflavin metabolites from bacteria presented by MR1 molecules. Alterations in gut microbiota have been reported in patients with type 1 diabetes (T1D), even before the onset of the disease. These changes can potentially alter the frequency or phenotype of circulating MAIT cells.

Methods: We characterized peripheral blood MAIT cells in a cohort of 51 children with newly diagnosed T1D, 35 at-risk children positive for multiple autoantibodies (AAb+) and 120 age-matched healthy children. Using multi-color flow cytometry, we analysed the frequency, surface phenotype and cytokine production of MAIT cells. In addition, we characterized the frequency and surface phenotype of blood MAIT cells in 26 patients with long-standing T1D and 25 age-matched healthy controls.

Results: No significant differences in MAIT cell frequency were observed between the study groups. Further phenotyping revealed that the expression of CD8, CD27, CCR5 and β7 integrin on MAIT cells was lower in children with newly diagnosed T1D compared to AAb+ and healthy children. However, none of these changes were observed in adult patients with long-standing T1D. The frequency of MAIT cells producing IFN-γ was also lower in children with newly diagnosed T1D, but the frequencies of IL-17A- and IL-4-secreting MAIT cells were similar in the study groups. Finally, the capacity of MAIT cells to be activated in vitro by E.coli bacteria through MR1 was comparable between the study groups.

Conclusion: Subtle alterations in circulating MAIT cells were observed in children at the diagnosis of T1D, but not in autoantibody-positive at-risk children, or in adult patients with long-standing disease. Consequently, the alterations in blood MAIT cells are likely associated with the clinical manifestation of the disease rather than being features of earlier T1D autoimmunity.