Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Diab-Q-Kit II: Next generation combinatorial nanotechnology for profiling islet autoreactive CD8 T-cells for immune memory and activation (#135)

Joana Abreu 1 , Marina Panarina 2 , Raivo Uibo 2 , Bart Roep 1
  1. Leiden University Medical Center, Leiden, Netherlands
  2. Immunology Group, IGMP, University of Tartu, Tartu, Estonia

We previously reported the design and validation of the Diab-Q-kit, a nanotechnology that allows the simultaneous detection of large arrays of islet-autoreactive CD8 T-cells directly from blood, based on the T-cell receptor specificity for its peptide-MHC ligand. This methodology has been employed to monitor islet transplant recipients, gene therapy and natural history of type 1 diabetes (T1D), and has been assigned ‘boutique assay’ status by the ITN. Currently the Diab-Q-kit is being validated internationally by the IDS T-Cell Workshop Committee. We have recently upgraded the Diab-Q-kit to allow characterization of the activation status of autoreactive T-cells through the inclusion of cell surface markers to distinguish naïve, effector and central memory T-cells. The inclusion of memory markers allowed to completely segregate T1D patients from healthy donors (p=0.02). Furthermore, analysis of T1D patients transplanted with islets showed that islet-specific CD8 T-cells are largely of a memory phenotype, underscoring the role of memory autoreactive CD8 T-cells after islet transplantation. To determine immune correlates of recurrent autoimmunity, we are currently investigating the phenotype of autoreactive CD8 T-cells found before and after islet transplantation in relapsing vs. remitting patients comparing thymoglobulin and alemtuzumab as transplantation induction therapies, and sort naïve and memory islet autoreactive CD8 T-cells for RNA sequencing in relation with autoreactivity and activation status.