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Diabetes. 2019 Mar 20. pii: db181081. doi: 10.2337/db18-1081. [Epub ahead of print]

Dynamic Immune Phenotypes of B and T Helper Cells Mark Distinct Stages of T1D Progression.

Author information

1
Translational Research Program, Benaroya Research Institute, Seattle, WA, 98101, USA.
2
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
3
Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, 98101, USA.
4
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, 98101, USA; jbuckner@benaroyaresearch.org drawling@u.washington.edu.
5
Departments of Pediatrics and Immunology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
6
Translational Research Program, Benaroya Research Institute, Seattle, WA, 98101, USA; jbuckner@benaroyaresearch.org drawling@u.washington.edu.

Abstract

Multiple studies of B and T cell compartments and their response to stimuli demonstrate alterations in established Type 1 Diabetes (T1D). Yet it is not known whether these alterations reflect immune mechanisms that initiate islet autoimmunity, promote disease progression or are secondary to disease. To address these questions, we utilized samples from the TrialNet Pathway to Prevention study to investigate T cell responses to IL-2 and Treg mediated suppression, the composition of the B cell compartment, and B cell responses to BCR and IL-21 receptor engagement. These studies revealed stage-dependent T- and B cell functional and immune phenotypes; namely early features that differentiate autoantibody-positive (autoAb+) at-risk first-degree relatives (FDRs) from autoAbneg FDR and persisted through clinical diagnosis; late features that arose at or near T1D diagnosis; and dynamic features that were enhanced early and blunted at later disease stages, indicating evolving responses along the continuum of T1D. We further explored how these specific phenotypes are influenced by therapeutic interventions. Our integrated studies provide unique insights into stable and dynamic stage-specific immune states and define novel immune phenotypes of potential clinical relevance.

PMID:
30894366
DOI:
10.2337/db18-1081

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