CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes

Fox, 2006, Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study, Circulation, 113, 2914, 10.1161/CIRCULATIONAHA.106.613828 Gale, 2002, The rise of childhood type 1 diabetes in the 20th century, Diabetes, 51, 3353, 10.2337/diabetes.51.12.3353 Eisenbarth, 1986, Type I diabetes mellitus. A chronic autoimmune disease, N Engl J Med, 314, 1360, 10.1056/NEJM198605223142106 Rahier, 2008, Pancreatic beta-cell mass in European subjects with type 2 diabetes, Diabetes Obes Metab, 10, 32, 10.1111/j.1463-1326.2008.00969.x Saisho, 2007, Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes, Clin Anat, 20, 933, 10.1002/ca.20543 Pietropaolo, 2000, Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes, Diabetes, 49, 32, 10.2337/diabetes.49.1.32 Winer, 2011, B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies, Nat Med, 17, 610, 10.1038/nm.2353 Mallone, 2013, Biomarkers for immune intervention trials in type 1 diabetes, Clin Immunol, 149, 286, 10.1016/j.clim.2013.02.009 Arif, 2004, Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health, J Clin Invest, 113, 451, 10.1172/JCI19585 Long, 2010, Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects, Diabetes, 59, 407, 10.2337/db09-0694 Penaranda, 2011, Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells, J Immunol, 187, 2015, 10.4049/jimmunol.1100713 Velthuis, 2010, Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC-multimers, Diabetes, 59, 1721, 10.2337/db09-1486 Roep, 2010, Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes, Nat Rev Immunol, 10, 145, 10.1038/nri2705 von Herrath, 2007, Type 1 diabetes as a relapsing-remitting disease?, Nat Rev Immunol, 7, 988, 10.1038/nri2192 Sanda, 2008, Islet antigen specific IL-10+ immune responses but not CD4+CD25+FoxP3+ cells at diagnosis predict glycemic control in type 1 diabetes, Clin Immunol, 127, 138, 10.1016/j.clim.2007.12.003 Oseroff, 2012, T cell responses to known allergen proteins are differently polarized and account for a variable fraction of total response to allergen extracts, J Immunol, 189, 1800, 10.4049/jimmunol.1200850 Fennessy, 1994, A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population. Childhood Diabetes in Finland (DiMe) Study Group, Diabetologia, 37, 937, 10.1007/BF00400951 Nerup, 1974, HL-A antigens and diabetes mellitus, Lancet, 2, 864, 10.1016/S0140-6736(74)91201-X Park, 1998, Combinations of HLA DR and DQ molecules determine the susceptibility to insulin-dependent diabetes mellitus in Koreans, Hum Immunol, 59, 794, 10.1016/S0198-8859(98)00076-7 Brooks-Worrell, 2011, Identification of autoantibody-negative autoimmune type 2 diabetic patients, Diabetes Care, 34, 168, 10.2337/dc10-0579 Cnop, 2005, Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities, Diabetes, 54, S97, 10.2337/diabetes.54.suppl_2.S97 Carlsson, 2009, Topology and data, Bull Am Math Soc, 46, 255, 10.1090/S0273-0979-09-01249-X Lum, 2013, Extracting insights from the shape of complex data using topology, Sci Reports, 3, 1236, 10.1038/srep01236 Gloyn, 2001, Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53), Diabet Med, 18, 206, 10.1046/j.1464-5491.2001.00449.x Gloyn, 2003, Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes, Diabetes, 52, 568, 10.2337/diabetes.52.2.568 Hani, 1998, Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians, Diabetologia, 41, 1511, 10.1007/s001250051098 Filippi, 2005, How viral infections affect the autoimmune process leading to type 1 diabetes, Cell Immunol, 233, 125, 10.1016/j.cellimm.2005.04.009 Filippi, 2008, Viral trigger for type 1 diabetes: pros and cons, Diabetes, 57, 2863, 10.2337/db07-1023 Coppieters, 2012, Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients, J Exp Med, 209, 51, 10.1084/jem.20111187 Skog, 2013, Revisiting the notion of type 1 diabetes being a T-cell-mediated autoimmune disease, Curr Opin Endocrinol Diabetes Obes, 20, 118, 10.1097/MED.0b013e32835edb89 Keenan, 2010, Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study, Diabetes, 59, 2846, 10.2337/db10-0676