TCR Bias of In Vivo Expanded T Cells in Pancreatic Islets and Spleen at the Onset in Human Type 1 Diabetes

摘要: Autoreactive T cells, responsible for the destruction of pancreatic β cells in type 1 diabetes, are known to have a skewed TCR repertoire NOD mouse. To define autoreactive cell human we searched intraislet monoclonal expansions from recent onset pancreas then trace them down patient's peripheral blood and spleen. Islet infiltration was diverse, but five β-chain variable were detected Vβ1, Vβ7, Vβ11, Vβ17, Vβ22 families. identify any sequence bias TCRs intrapancreatic analyzed 139 different CDR3 sequences. We observed amino acid preferences NDN region that suggested within infiltrating cells. The expanded sequences contained combinations fit bias. Using these as marker, traced some There, identified expansion with identical found islets polyclonal repertoire. same PBMCs, making cross talk between spleen reflected evident. No other or spleen, suggesting clone may accumulated situ by an autoantigen present both pancreas. Thus, might be contributing disease perpetuation expanding retaining