Reduced PD-1 expression on circulating follicular and conventional FOXP3+ Treg cells in children with new onset type 1 diabetes and autoantibody-positive at-risk children
Copyright © 2019 Elsevier Inc. All rights reserved.
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 211(2020) vom: 15. Feb., Seite 108319 |
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Weitere Verfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2020
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Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't AAb-negative AAb-positive Autoantibodies (AAb) CXCL13 Follicular Treg cells PD-1 Regulatory T cells (Treg) mehr... |
Zusammenfassung: | Copyright © 2019 Elsevier Inc. All rights reserved. Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and conventional (CXCR5-) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice |
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Beschreibung: | Date Completed 04.08.2020 Date Revised 20.08.2020 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2019.108319 |