Format

Send to

Choose Destination
PLoS One. 2018 Aug 8;13(8):e0200818. doi: 10.1371/journal.pone.0200818. eCollection 2018.

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

Author information

1
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
2
Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.
3
Computer Graphics and Visualization, Delft University of Technology, Delft, the Netherlands.
4
Department of LKEB Radiology, Leiden University Medical Center, Leiden, the Netherlands.
5
Department of Diabetes Immunology, Diabetes & Metabolism Research Institute at the Beckman Research Institute, City of Hope, Duarte, California, United States of America.

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.

PMID:
30089176
PMCID:
PMC6082515
DOI:
10.1371/journal.pone.0200818
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center