Frequencies of CD8 and DN MAIT Cells Among Children Diagnosed With Type 1 Diabetes Are Similar to Age-Matched Controls.

Robert Z Harms,Earline Edwards,Victoria B Smith,Monina Cabrera,Katie R Ostlund,Nora Sarvetnick,Lynette M Smith

doi:10.3389/fimmu.2021.604157

Abstract

Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

Highlights

In human populations across the globe, modern living conditions have been associated with increased incidence and prevalence of various forms of autoimmunity, including type 1 diabetes (T1D) [1, 2]
When comparing juvenile T1D subjects with controls, we observed no significant changes in frequency of either CD8 or double negative (DN) Mucosal-associated invariant T (MAIT) cells (Figure 1A and Table 1)
We found no significant correlations among MAIT cell frequencies and levels of autoantibodies for islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65), insulinoma antigen 2 (IA-2), and zinc transporter 8 (ZNT8) (T1D subjects: Figures 2A–D; control subjects: Supplementary Figures 3A–D)

Summary

Introduction

In human populations across the globe, modern living conditions have been associated with increased incidence and prevalence of various forms of autoimmunity, including type 1 diabetes (T1D) [1, 2]. Pathogenic microbial imbalances are thought to lead to mucosal inflammation and enterocyte damage, and, to increased exposure to microbial products and infectious agents Such exposure has been postulated to promote the breakdown of immunological tolerance, as well as negatively impact beta cell health by creating an inflammatory environment in and around the pancreatic islets [3, 4]. Evidence for this theory includes histological findings of increased inflammation in the intestinal mucosa, elevated circulating zonulin, as well as several reports of distinct bacterial floras associated with T1D [5,6,7,8,9,10,11]

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