Altered CD161 bright CD8+ mucosal associated invariant T (MAIT)-like cell dynamics and increased differentiation states among juvenile type 1 diabetics.

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 CD161 bright 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.