Abstract
T-cell mediated autoimmune beta-cell destruction is an important component of type 1 diabetes (T1D) and insulin is a critical antigen recognized by autoreactive T-cells. The aim of this study was to investigate the precursor frequency of insulin reactive T-cells in type 1 diabetes. We studied 19 T1D patients, 12 age-matching non-diabetic healthy siblings and 12 non-diabetic healthy parents. Limiting dilution analysis (LDA) was performed to insulin and tetanus toxoid (TT). A progressive decrease in the number of negative cultures at increasing cell concentrations that is represented by a low goodness-of-fit (GoF, low Chi-square), was seen with the TT response in all three groups; precursor frequencies and GoF were similar in patients, siblings, and parents. Reactivity to insulin, however, showed low precursor frequencies in patients and siblings and the LDA to insulin demonstrated dramatic decreases in the number of positive cultures at higher cell concentrations leading to a high GoF in patients and siblings compared to parents. This saw-toothed pattern of reactivity to insulin is indicative of multiple hit kinetics and implies that the response is regulated. Consequently the precursor frequency of insulin autoreactive cells in...Continue Reading
References
Nov 1, 1992·European Journal of Clinical Investigation·B O Roep, R R De Vries
Jun 14, 1990·Nature·B O RoepJ C Hutton
Aug 1, 1990·Immunology Today·C E SharrockS Man
Oct 1, 1988·Diabetes Care·P VardiG S Eisenbarth
Dec 1, 1988·International Journal of Bio-medical Computing·L W StrijboschW A Buurman
Feb 26, 1987·Journal of Immunological Methods·L W StrijboschG Groenewegen
Jan 1, 1983·Springer Seminars in Immunopathology·K EichmannH U Weltzien
Mar 1, 1994·The Journal of Experimental Medicine·J ZhangD A Hafler
Nov 24, 1994·The New England Journal of Medicine·M A Atkinson, N K Maclaren
Jan 3, 1994·Journal of Immunological Methods·T Bonnefoix, J J Sotto
Dec 1, 1995·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·I KockumA Lernmark
Aug 14, 1996·Journal of Immunological Methods·T BonnefoixJ J Sotto
Sep 1, 1996·Diabetes·B O Roep
Oct 1, 1996·Diabetes·K Haskins, D Wegmann
May 1, 1997·Diabetologia·N C SchlootG S Eisenbarth
Nov 5, 1997·Diabetologia·H NoorchashmL C Harrison
Aug 17, 1999·The Journal of Clinical Investigation·S A LitherlandM J Clare-Salzler
Oct 4, 2000·Diabetes·H ReijonenG T Nepom
Mar 1, 2002·Journal of Autoimmunity·Ivana Durinovic-BellóAnette-G Ziegler
Apr 11, 2003·Diabetologia·Bart O Roep
Nov 20, 2003·Journal of Autoimmunity·Nanette C SchlootTimothy Tree
Jan 28, 2004·Diabetologia·I Durinovic-BellóB O Boehm
Feb 3, 2004·The Journal of Clinical Investigation·Sefina ArifMark Peakman
Sep 1, 1984·Immunology Today·I Lefkovits, H Waldmann
Oct 1, 1984·Immunology Today·H Waldmann, I Lefkovits
Citations
Jan 10, 2012·Nature Medicine·Bart O RoepFrauke Zipp
Apr 5, 2012·Cold Spring Harbor Perspectives in Medicine·Bart O Roep, Mark Peakman
May 9, 2012·Anatomy Research International·Norio KanatsunaAke Lenmark
Dec 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gabrielle G M PinkseBart O Roep
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Christine BeetonK George Chandy
Dec 24, 2008·Diabetologia·J H VelthuisB O Roep
Nov 5, 2011·Current Opinion in Immunology·Bart O Roep, Mark Peakman
Jun 4, 2011·Journal of Autoimmunity·Wendy W UngerBart O Roep
Oct 6, 2009·Journal of Autoimmunity·Isaac YanivJerry Stein
Feb 3, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Danny Zipris
Sep 14, 2007·Pediatric Diabetes·Zuzana VrabelovaKaterina Stechova
Feb 8, 2006·Annals of the New York Academy of Sciences·Francesco BoinAntony Rosen
Apr 12, 2012·Diabetes/metabolism Research and Reviews·A A Verrijn StuartB J Prakken
Jan 12, 2010·Clinical and Experimental Immunology·B O RoepF Dotta
Apr 2, 2010·Diabetes·Jurjen H VelthuisBart O Roep
Jan 29, 2014·Nature Reviews. Endocrinology·Bart O Roep, Timothy I M Tree
Apr 9, 2008·European Journal of Immunology·Todd Brusko, Jeffrey Bluestone
Aug 18, 2005·European Journal of Immunology·Ioana PredaSofia Casares
Aug 27, 2017·Diabetes·Justin A SpanierBrian T Fife
Dec 20, 2005·International Immunology·Heather L ZwickeyIra Mellman