Many individuals with cystic fibrosis (CF) develop diabetes or CF–related diabetes (CFRD).Some published data indicates that CFRD shares autoimmune phenotypes in common with type 1 diabetes (T1D). These include a higher prevalence of islet autoantibodies for CFRD patients than the general population and signs of broad immune dysregulation (including a Th17 signature). Notably, in autoantibody–positive CF patients, diabetes onset occurs earlier and is generally associated with a higher risk of acute complications. In a study funded by the Cystic Fibrosis Foundation, T cells from peripheral blood mononuclear cells from matched cohorts of individuals with CFRD, with CF, with T1D, and from controls are being examined for islet–reactivity and phenotype. Here, we propose to examine cryopreserved single cell suspensions of pancreatic draining lymph nodes from matched donors with CFRD, withT1D, and from donors without diabetes with and without pancreatitis (the latter serving as an inflammation control)for these paprameters. Our overall goal is to increase the understanding of the autoimmune response to islet–antigens in donors with CFRD and in T1Das compared to those from control and to those from donors with pancreatitis (inflammatory state)and from control donors and identify shared T cell specificities and immune mechanisms that might contribute to their decreased insulin secretion and beta cell damage in CFRD and T1D.
