SUMMIT 2018: Keynote Speaker Bart Roep

Dr. Bart O. Roep is Chair and Professor of Department of Diabetes Immunology, and holds the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes at the Diabetes & Metabolism Research Institute at the Beckman Research Institute of the City of Hope in Los Angeles. He is also Professor of Medicine, Professor of Diabetology, Immunopathology & Intervention and Director of the National Diabetes Center of Excellence at the Leiden University Medical Center in The Netherlands and Visiting Professor of the Danish Diabetes Academy. After studying medical sciences and medicine at the University of Amsterdam, he obtained his PhD in medicine at the Leiden University Medical Center. He discovered the role of T cells in diabetes and focused on defining human cellular immune responses, autoantigen identification, and islet transplantation and the design, execution and immunological monitoring of immune intervention strategies in clinical type 1 diabetes and beta-cell replacement therapies, including pioneering trials on tissue-specific tolerance induction, gene and stem cell therapy. He is founder and director of the national platform for clinical immune intervention therapy in The Netherlands and published more than 350 original articles on his discoveries. He received many prestigious awards, including the Minkowski Prize, the VICI award and a Fellowship of the Royal Dutch Academy of Arts and Sciences.

“Deep phenotyping of islet autoreactive and immunoregulatory T-cells in type 1 diabetes”

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 auto‐ (pre‐proinsulin), neo‐ (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 characterize 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. Using a different panel of markers we were able to identify regulatory and effector T‐cells induced by priming with tolerogenic dendritic cells pulsed with proinsulin peptide, which led to the discovery of biomarkers to be monitored in our clinical trial.