Precursor frequencies of T-cells reactive to insulin in recent onset type 1 diabetes mellitus

Journal of Autoimmunity
Ramachandra G NaikBart O Roep

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
Aug 1, 1990·Immunology Today·C E SharrockS Man
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
Nov 24, 1994·The New England Journal of Medicine·M A Atkinson, N K Maclaren
Dec 1, 1995·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·I KockumA Lernmark
Oct 1, 1996·Diabetes·K Haskins, D Wegmann
Nov 5, 1997·Diabetologia·H NoorchashmL C Harrison
Aug 17, 1999·The Journal of Clinical Investigation·S A LitherlandM J Clare-Salzler
Mar 1, 2002·Journal of Autoimmunity·Ivana Durinovic-BellóAnette-G Ziegler
Feb 3, 2004·The Journal of Clinical Investigation·Sefina ArifMark Peakman
Oct 1, 1984·Immunology Today·H Waldmann, I Lefkovits

❮ Previous
Next ❯

Citations

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
Nov 5, 2011·Current Opinion in Immunology·Bart O Roep, Mark Peakman
Oct 6, 2009·Journal of Autoimmunity·Isaac YanivJerry Stein
Feb 3, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Danny Zipris
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
Jan 29, 2014·Nature Reviews. Endocrinology·Bart O Roep, Timothy I M Tree
Apr 9, 2008·European Journal of Immunology·Todd Brusko, Jeffrey Bluestone
Dec 20, 2005·International Immunology·Heather L ZwickeyIra Mellman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.