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Monti, P.* ; Scirpoli, M.* ; Rigamonti, A.* ; Mayr, A.* ; Jaeger, A.* ; Bonfanti, R.* ; Chiumello, G.* ; Ziegler, A.-G.* ; Bonifacio, E.*

Evidence for in vivo primed and expanded autoreactive T cells as a specific feature of patients with type 1 diabetes.

J. Immunol. 179, 5785-5792 (2007)
PMC
Open Access Green as soon as Postprint is submitted to ZB.
Identifying beta cell autoantigen-reactive T cells that are involved in the pathogenesis of type 1 diabetes has been troublesome for many laboratories. Disease-relevant autoreactive T cells should be in vivo Ag experienced. The aim of this study was to test this hypothesis and then use this principle as a strategy for identifying diabetes-relevant autoreactive T cells. In this study, a CSFE dilution assay was used to detect glutamic acid decarboxylase 65 (GAD65)- and insulin-responsive T cells and HLA-0201*-GAD65(114-122) pentamers were used to detect CD8(+) GAD-responsive T cells in memory CD45RO(+) and naive CD45RO(-) cell populations from patients with type 1 diabetes and healthy control subjects. T cell proliferative history was evaluated by flow cytometry telomere length measurement. CD4(+) and CD8(+) T cells specific for GAD65 and insulin were present in patients with type 1 diabetes and control subjects. Within the naive CD45RO(-) cells, CD4(+) and CD8(+) T cell responses were similar between patients and controls. Within the memory CD45RO(+) cells, CD4(+) T cell responses against whole GAD65 and insulin and HLA-0201*-GAD65(114-122) pentamer-positive CD8(+) T cells were found in patients with type 1 diabetes, but not in control subjects (p < 0.05 for all). Responding cells from the CD45RO(+) T cell population had substantially shorter telomere lengths than responding cells from the CD45RO(-) cell population. Diabetes-specific autoreactive T cells in the circulation have uniquely undergone sustained in vivo proliferation and differentiation into memory T cells. Prior selection of these cells is possible and is a way to identify diabetes-relevant target Ags and epitopes.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Journal Journal of Immunology
Quellenangaben Volume: 179, Issue: 9, Pages: 5785-5792 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)