Islet-cell antigen-reactive T cells show different expansion rates and Th1/Th2 differentiation in type 1 diabetic patients and healthy controls |
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Authors: | Ott Patrick A Herzog Bernhard A Quast Stefan Hofstetter Harald H Boehm Bernhard O Tary-Lehmann Magdalena Durinovic-Bello Ivana Berner Beate R Lehmann Paul V |
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Affiliation: | Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. |
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Abstract: | 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. |
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Keywords: | Islet-cell antigen-reactive T cells Th1/Th2 differentiation Type 1 diabetes |
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