TY - JOUR
T1 - Frequencies of CD8 and DN MAIT Cells Among Children Diagnosed With Type 1 Diabetes Are Similar to Age-Matched Controls
AU - Harms, Robert Z.
AU - Ostlund, Katie R.
AU - Cabrera, Monina
AU - Edwards, Earline
AU - Smith, Victoria B.
AU - Smith, Lynette M.
AU - Sarvetnick, Nora
N1 - Publisher Copyright:
© Copyright © 2021 Harms, Ostlund, Cabrera, Edwards, Smith, Smith and Sarvetnick.
PY - 2021/2/23
Y1 - 2021/2/23
N2 - 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.
AB - 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.
KW - autoantibodies
KW - human cytomegalovirus
KW - interleukin 18
KW - interleukin 7
KW - mucosal associated invariant T cells
KW - type 1 diabetes
KW - vitamin D
UR - http://www.scopus.com/inward/record.url?scp=85102363227&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102363227&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.604157
DO - 10.3389/fimmu.2021.604157
M3 - Article
C2 - 33708202
AN - SCOPUS:85102363227
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 604157
ER -