Islet-cell antigen-reactive T cells show different expansion rates and Th1/Th2 differentiation in type 1 diabetic patients and healthy controls

The low frequency of islet-cell antigen-reactive T cells in type 1 diabetes makes their direct measurement difficult. Commonly used in vitro expansion could alter in vivo frequencies and Th1/Th2 differentiation states. Using IFN-gamma/IL-4 double color ELISPOT, we tested longitudinally the reactivit...

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Détails bibliographiques
Publié dans:	Clinical immunology (Orlando, Fla.). - 1999. - 115(2005), 1 vom: 07. Apr., Seite 102-14
Auteur principal:	Ott, Patrick A (Auteur)
Autres auteurs:	Herzog, Bernhard A, Quast, Stefan, Hofstetter, Harald H, Boehm, Bernhard O, Tary-Lehmann, Magdalena, Durinovic-Bello, Ivana, Berner, Beate R, Lehmann, Paul V
Format:	Article
Langue:	English
Publié:	2005
Accès à la collection:	Clinical immunology (Orlando, Fla.)
Sujets:	Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Autoantigens Isoenzymes Membrane Proteins Peptide Fragments Interleukin-4 207137-56-2 plus... Interferon-gamma 82115-62-6 Proinsulin 9035-68-1 PTPRN protein, human EC 3.1.3.48 Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases Receptor-Like Protein Tyrosine Phosphatases, Class 8 Glutamate Decarboxylase EC 4.1.1.15 glutamate decarboxylase 2

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Résumé:	The low frequency of islet-cell antigen-reactive T cells in type 1 diabetes makes their direct measurement difficult. Commonly used in vitro expansion could alter in vivo frequencies and Th1/Th2 differentiation states. Using IFN-gamma/IL-4 double color ELISPOT, we tested longitudinally the reactivity of PBMC from HLA-matched diabetic patients and healthy controls to GAD65, IA-2, and proinsulin peptides ex vivo and after in vitro culture. The peptide-reactive T cells showed IFN-gamma bias in the patients' PBMC in the primary assay. During in vitro culture, both IFN-gamma- and IL-4-producing cells were induced in controls, suggesting that the precursor cells were uncommitted naive T cells in vivo. In contrast, in diabetic patients, the ex vivo IFN-gamma response was conserved during culture, suggesting their Th1 commitment. Using CFSE-dye-dilution, we demonstrate that naive T cells expand in vitro at a faster rate than memory cells, which might account for the differences in expansion rates between diabetic patients and controls
Description:	Date Completed 30.06.2005 Date Revised 21.11.2008 published: Print Citation Status MEDLINE
ISSN:	1521-7035