GM-CSF producing autoreactive CD4+ T cells in type 1 diabetes

GM-CSF producing autoreactive CD4+ T cells in type 1 diabetes The phenotype of autoreactive T cells in type 1 diabetes is described as Th1, Th17 and/or Th21, but is largely uncharacterized. We combined multi-parameter cytokine profiling and proliferation, and identified GM-CSF producing cells as a component of the response to beta cell autoantigens proinsulin and GAD65. Overall cytokine profiles of CD4+ T cell were not altered in type 1 diabetes. In contrast, patients with recent onset type 1 diabetes had increased frequencies of proinsulin-responsive CD4+CD45RA− T cells producing GM-CSF (p=0.002), IFNγ (p=0.004), IL-17A (p=0.008), IL-21 (p=0.011), and IL-22 (p=0.007), and GAD65-responsive CD4+CD45RA− T cells producing IL-21 (p=0.039). CD4+ T cells with a GM-CSF+IFNγ−IL-17A−IL-21−IL-22− phenotype were increased in patients for responses to both proinsulin (p=0.006) and GAD65 (p=0.037). GM-CSF producing T cells are a novel phenotype in the repertoire of T helper cells in type 1 diabetes and consolidate a Th1/Th17 pro-inflammatory pathogenesis in the disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Immunology Elsevier

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Publisher
Elsevier
Copyright
Copyright © 2017 The Authors
ISSN
1521-6616
D.O.I.
10.1016/j.clim.2017.12.002
Publisher site
See Article on Publisher Site

Abstract

The phenotype of autoreactive T cells in type 1 diabetes is described as Th1, Th17 and/or Th21, but is largely uncharacterized. We combined multi-parameter cytokine profiling and proliferation, and identified GM-CSF producing cells as a component of the response to beta cell autoantigens proinsulin and GAD65. Overall cytokine profiles of CD4+ T cell were not altered in type 1 diabetes. In contrast, patients with recent onset type 1 diabetes had increased frequencies of proinsulin-responsive CD4+CD45RA− T cells producing GM-CSF (p=0.002), IFNγ (p=0.004), IL-17A (p=0.008), IL-21 (p=0.011), and IL-22 (p=0.007), and GAD65-responsive CD4+CD45RA− T cells producing IL-21 (p=0.039). CD4+ T cells with a GM-CSF+IFNγ−IL-17A−IL-21−IL-22− phenotype were increased in patients for responses to both proinsulin (p=0.006) and GAD65 (p=0.037). GM-CSF producing T cells are a novel phenotype in the repertoire of T helper cells in type 1 diabetes and consolidate a Th1/Th17 pro-inflammatory pathogenesis in the disease.

Journal

Clinical ImmunologyElsevier

Published: Mar 1, 2018

References

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