Charakterisierung der CD8 T-Zellen im humanen Typ-1 Diabetes
Zusammenfassung der Projektergebnisse
Autoreactive T cells targeting antigenic epitopes are considered the main mediators of beta cell destruction in type 1 diabetes (T1D). Previously, using HLA-A2 tetramers, our team was the first to demonstrate the presence of antigen-specific CD8+ T cells in-situ in islets from pancreata from organ donors with T1D. Here, our overall objective was to clearly define numbers and precise location of PPI15-24–specific CD8+ T cells during diabetes development in pancreas tissue sections received from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Interestingly, cellular infiltration was increased in the exocrine pancreas already in singleautoantibody positive individuals without clinical disease with PPI15–24-specific CD8+ T cells accounting for .48.37±4.3% of CD8+ T cells. While this relative frequency of PPI15–24-specific CD8 T cells was constant in the exocrine pancreas regardless of the disease state, their presence within insulin-containing islets (but not islets devoid of insulin) was significantly increased up to 14.8-fold accounting sometimes for up to 70.88 % of all CD8+ T cells. Additionally, their presence in proximity to insulin-containing islets was up to 4.2-fold accounting sometimes for up to 74.59% of all CD8+ T cells, which indicates that beta cells might attract their perpetrators over time. Our findings constitute the first spatial quantitation of PPI15–24-specific CD8+ T cells in the human pancreas and further highlight their potential importance as key effector T cells in beta cell destruction. The funded project provides important information on the pathogenesis of human T1D and may lead to additional opportunities for novel therapies.
