Heterogeneity of circulating CD8 T-cells specific to islet, neo-antigen and virus in patients with type 1 diabetes mellitus

Sandra Laban (Corresponding author), Jessica S. Suwandi (Corresponding author), Vincent van Unen, Jos Pool, Joris Wesselius, Thomas Höllt, Nicola Pezzotti, Anna Vilanova, Boudewijn P.F. Lelieveldt, Bart O. Roep (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)
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Auto-reactive CD8 T-cells play an important role in the destruction of pancreatic β-cells resulting in type 1 diabetes (T1D). However, the phenotype of these auto-reactive cytolytic CD8 T-cells has not yet been extensively described. We used high-dimensional mass cytometry to phenotype autoantigen- (pre-proinsulin), neoantigen- (insulin-DRIP) and virus-(cytomegalovirus) reactive CD8 T-cells in peripheral blood mononuclear cells (PBMCs) of T1D patients. A panel of 33 monoclonal antibodies was designed to further characterise these cells at the single-cell level. HLA-A2 class I tetramers were used for the detection of antigen-specific CD8 T-cells. Using a novel Hierarchical Stochastic Neighbor Embedding (HSNE) tool (implemented in Cytosplore), we identified 42 clusters within the CD8 T-cell compartment of three T1D patients and revealed profound heterogeneity between individuals, as each patient displayed a distinct cluster distribution. Single-cell analysis of pre-proinsulin, insulin-DRIP and cytomegalovirus-specific CD8 T-cells showed that the detected specificities were heterogeneous between and within patients. These findings emphasize the challenge to define the obscure nature of auto-reactive CD8 T-cells.

Original languageEnglish
Article numbere0200818
Number of pages15
JournalPLoS ONE
Issue number8
Publication statusPublished - 1 Aug 2018
Externally publishedYes


  • Adult
  • Autoantigens/immunology
  • Biomarkers/blood
  • CD8-Positive T-Lymphocytes/cytology
  • Diabetes Mellitus, Type 1/immunology
  • Female
  • HLA-A2 Antigen/immunology
  • Humans
  • Insulin-Secreting Cells/immunology
  • Leukocytes, Mononuclear/immunology
  • Male
  • Phenotype
  • Single-Cell Analysis/methods


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