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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...
Show moreAuto-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.
Show less- All authors
- Laban, S.; Suwandi, J.S.; Unen, V. van; Pool, J.; Wesselius, J.; Hollt, T.; Pezzotti, N.; Vilanova, A.; Lelieveldt, B.P.F.; Roep, B.O.
- Date
- 2018
- Journal
- PLoS ONE