Abnormal T cell frequencies, including cytomegalovirus - Associated expansions, distinguish seroconverted subjects at risk for type 1 diabetes

Robert Z. Harms, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Victoria B. Smith, Lynette M. Smith, Peter Gottlieb, Nora Sarvetnick

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted subjects, associated with IA-2 levels, and most elevated among CMV+ seroconverted subjects who progressed to disease. Combined, our data indicate discrete, yet profound T cell alterations are associated with islet autoimmunity among at-risk subjects.

Original languageEnglish (US)
Article number2332
JournalFrontiers in immunology
Volume9
Issue numberOCT
DOIs
StatePublished - Oct 22 2018

Keywords

  • Autoimmunity
  • CD4 T cells
  • CD8 T cells
  • Cytomegalovirus-HCMV
  • Mucosal associated invariant T cells (MAIT)
  • T regulatory cells (Treg)
  • TrialNet
  • Type 1 diabetes (T1D)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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