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.

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@article{ bib:2018_plos_circulating_t_cells,
    author = {Sandra Laban and Jessica S. Suwandi and Vincent van Unen and Jos Pool and Joris Wesselius and Thomas H{\"o}llt and Nicola Pezzotti and Anna Vilanova and Boudewijn Lelieveldt and Bart O. Roep},
    title = { Heterogeneity of Circulating CD8 T-cells Specific to Islet, Neo-antigen and Virus in Patients with Type 1 Diabetes Mellitus },
    journal = { PLOS one },
    volume = { 13 },
    number = { 8 },
    pages = { e0200818 },
    year = { 2018 },
    doi = { 10.1371/journal.pone.0200818 },
}