| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Telethon-Juvenile Diabetes Research Foundation Center for Beta Cell Replacement, San Raffaele Scientific Institute, Milan, Italy;
Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy; and
Diabetes Research Institute, Munich, Germany
Identifying 
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*-GAD65114–122 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*-GAD65114–122 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Telethon Italy and the Juvenile Diabetes Research Foundation (JT-01, 1-2006-665), and by the Italian Ministry of Health (RF2004 N. 123). P.M. is a fellow of the Vita e Salute San Raffaele University PhD Programme in Molecular Medicine.
2 Address correspondence and reprint requests to Dr. Ezio Bonifacio at the current address: Center for Regenerative Therapies-Dresden, Dresden University of Technology, Tatzberg 47/49, 01307 Dresden, Germany. E-mail address: ezio.bonifacio{at}crt-dresden.de
3 Abbreviations used in this paper: T1DM, type I diabetes mellitus; GAD65, glutamic acid decarboxylase 65; PNA, peptide nucleic acid probe; IQR, interquartile range; FSC, forward scatter; SSC, side scatter; MFI, mean fluorescence intensity; TT, tetanus toxoid; LFU, level of flocculation units.
This article has been cited by other articles:
|
|
 |
|
  A. L. Putnam, T. M. Brusko, M. R. Lee, W. Liu, G. L. Szot, T. Ghosh, M. A. Atkinson, and J. A. Bluestone Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes Diabetes, March 1, 2009; 58(3): 652 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Galletti, C. Canones, P. Morande, M. Borge, P. Oppezzo, J. Geffner, R. Bezares, R. Gamberale, and M. Giordano Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia J. Immunol., September 1, 2008; 181(5): 3674 - 3683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Monti, M. Scirpoli, P. Maffi, L. Piemonti, A. Secchi, E. Bonifacio, M.-G. Roncarolo, and M. Battaglia Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4+CD25+FOXP3+ Regulatory T-Cells Diabetes, September 1, 2008; 57(9): 2341 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Martinuzzi, G. Novelli, M. Scotto, P. Blancou, J.-M. Bach, L. Chaillous, G. Bruno, L. Chatenoud, P. van Endert, and R. Mallone The Frequency and Immunodominance of Islet-Specific CD8+ T-cell Responses Change after Type 1 Diabetes Diagnosis and Treatment Diabetes, May 1, 2008; 57(5): 1312 - 1320. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
