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

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.

@Article { LSVPWHPVLR18,
  author       = "Laban, Sandra and Suwandi, Jessica S. and Unen, Vincent van and Pool, Jos and Wesselius, Joris and H\öllt,
                  Thomas and Pezzotti, Nicola and Vilanova, Anna and Lelieveldt, Boudewijn P.F. and Roep, Bart O.",
  title        = "Heterogeneity of circulating CD8 T-cells specific to islet, neo-antigen and virus in patients with type 1
                  diabetes mellitus",
  journal      = "PLoS ONE",
  number       = "8",
  volume       = "13",
  pages        = "e0200818",
  month        = "aug",
  year         = "2018",
  url          = "http://graphics.tudelft.nl/Publications-new/2018/LSVPWHPVLR18"
}