Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects

Journal of Autoimmunity
Bernhard A HerzogIvana Durinovic-Bello

Abstract

Active T cell recognition of islet antigens has been postulated as the pathogenic mechanism in human type 1 diabetes, but evidence is scarce. If T cells are engaged, they are expected to display increased clonal size and exhibit a T helper (Th)1/Th2 differentiation state. We used a peptide library that covers tyrosine phosphatase IA-2, a target antigen expressed in pancreatic beta cells, to probe 8 diabetic patients and 5 HLA-matched controls. When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. An average of 9 peptides was recognized in the patients vs. one in the controls. Determinant recognition primarily involved CD4+ cells and showed high variability among the patients. Furthermore, anti-CD28 antibody signal enhances quantitative assessment of effector T cells in T1D patients. In vitro expansion with peptides and IL-2 results in detection of responding cells in the controls and loss of disease specificity of the T cell response. Together these data provide strong evidence for the active targeting of IA-2 by Th1 memory effector cells in human t...Continue Reading

References

Jan 1, 1991·The Journal of Experimental Medicine·S Ehlers, K A Smith
Oct 1, 1996·Diabetologia·S GenoveseE Bonifacio
Jun 6, 1998·The Journal of Experimental Medicine·A J McMichael, C A O'Callaghan
Feb 23, 1999·Diabetologia·R D LeslieA L Notkins
Nov 24, 1999·The Journal of Clinical Investigation·M PeakmanR M Chicz
Oct 21, 2000·Journal of Autoimmunity·S BaekkeskovS Kash
Mar 1, 2002·Journal of Autoimmunity·Ivana Durinovic-BellóAnette-G Ziegler

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Citations

May 5, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Patrick A OttPaul V Lehmann
Sep 16, 2015·Current Diabetes Reports·John W McGintyEddie A James
Apr 25, 2016·Cancer Immunology, Immunotherapy : CII·Ioana MoldovanPaul V Lehmann
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Junbao YangWilliam W Kwok
Apr 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·MyLinh DangHoward W Davidson

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