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Mass Cytometry Identifies Distinct Subsets of Regulatory T Cells and Natural Killer Cells Associated With High Risk for Type 1 Diabetes
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 982Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin producing beta-cells. The time from onset of islet autoimmunity to manifest clinical disease can vary widely in length, and it is fairly uncharacterized both clinically and immunologically. In the current study, peripheral blood mononuclear cells from autoantibody-positive children with high risk for T1D, and from age-matched healthy individuals, were analyzed by mass cytometry using a panel of 32 antibodies. Surface markers were chosen to identify multiple cell types including T, B, NK, monocytes, and DC, and antibodies specific for identification of differentiation, activation and functional markers were also included in the panel. By applying dimensional reduction and computational unsupervised clustering approaches, we delineated in an unbiased fashion 132 phenotypically distinct subsets within the major immune cell populations. We were able to identify an effector memory Treg subset expressing HLA-DR, CCR4, CCR6, CXCR3, and GATA3 that was increased in the high-risk group. In addition, two subsets of NK cells defined by CD16(+) CD8(+) CXCR3(+) and CD16(+) CD8(+) CXCR3(+) CD11c(+) were also higher in the same subjects. High-risk individuals did not show impaired glucose tolerance at the time of sampling, suggesting that the changes observed were not the result of metabolic imbalance, and might be potential biomarkers predictive of T1D.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 10, article id 982
Keywords [en]
type 1 diabetes (T1D); high-risk for T1D; autoantibody-positive children; mass cytometry (CyTOF); regulatory T cells; NK cells
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-157531DOI: 10.3389/fimmu.2019.00982ISI: 000467335300001PubMedID: 31130961OAI: oai:DiVA.org:liu-157531DiVA, id: diva2:1328780
Note

Funding Agencies|Swedish Research Council (Vetenskapsradet); Swedish Child Diabetes Foundation (Barndiabetesfonden); Medical Research Council of Southeast Sweden (Forskningsradet i sydostra Sverige, FORSS); Novo Nordisk Foundation; ALF Grants, Region Ostergotland

Available from: 2019-06-23 Created: 2019-06-23 Last updated: 2019-11-04

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Barcenilla, HugoÅkerman, LindaPihl, MikaelLudvigsson, JohnnyCasas, Rosaura
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Division of Children's and Women's healthFaculty of Medicine and Health SciencesDepartment of Clinical Immunology and Transfusion MedicineDivision of Hematopoiesis and Developmental BiologyH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala
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