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

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

Research output: Contribution to journalArticleScientificpeer-review

7 Citations (Scopus)
13 Downloads (Pure)

Abstract

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
Pages (from-to)1-15
Number of pages15
JournalPLoS ONE
Volume13
Issue number8
DOIs
Publication statusPublished - 2018

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