| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and Immunology and
Medicine (Division of Endocrinology), Albert Einstein College of Medicine, Bronx, NY 10461;
Department of Microbiology and Infectious Diseases and Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Health Sciences Centre, Calgary, Canada; and
The Jackson Laboratory, Bar Harbor, ME 04609
Spontaneous autoimmune diabetes development in NOD mice requires both CD8+ and CD4+ T cells. Three pathogenic CD8+ T cell populations (represented by the G9C8, 8.3, and AI4 clones) have been described. Although the Ags for G9C8 and 8.3 are known to be insulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein, respectively, only mimotope peptides had previously been identified for AI4. In this study, we used peptide/MHC tetramers to detect and quantify these three pathogenic populations among 
cell-reactive T cells cultured from islets of individual NOD mice. Even within age-matched groups, each individual mouse exhibited a unique distribution of cell-reactive CD8+ T cells, both in terms of the number of tetramer-staining populations and the relative proportion of each population in the islet infiltrate. Thus, the inflammatory process in each individual follows its own distinctive course. Screening of a combinatorial peptide library in positional scanning format led to the identification of a peptide derived from dystrophia myotonica kinase (DMK) that is recognized by AI4-like T cells. Importantly, the antigenic peptide is naturally processed and presented by DMK-transfected cells. DMK is a widely expressed protein that is nonetheless the target of a cell-specific autoimmune response.
This article has been cited by other articles:
|
|
 |
|
  L. Li, B. Wang, J. A. Frelinger, and R. Tisch T-Cell Promiscuity in Autoimmune Diabetes Diabetes, August 1, 2008; 57(8): 2099 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Papewalis, M. Wuttke, J. Seissler, Y. Meyer, C. Kessler, B. Jacobs, E. Ullrich, H. S. Willenberg, S. Schinner, T. Baehring, et al. Dendritic Cell Vaccination with Xenogenic Polypeptide Hormone Induces Tumor Rejection in Neuroendocrine Cancer Clin. Cancer Res., July 1, 2008; 14(13): 4298 - 4305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mukhopadhaya, T. Hanafusa, I. Jarchum, Y.-G. Chen, Y. Iwai, D. V. Serreze, R. M. Steinman, K. V. Tarbell, and T. P. DiLorenzo Selective delivery of {beta} cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice PNAS, April 29, 2008; 105(17): 6374 - 6379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Enee, E. Martinuzzi, P. Blancou, J.-M. Bach, R. Mallone, and P. van Endert Equivalent Specificity of Peripheral Blood and Islet-Infiltrating CD8+ T Lymphocytes in Spontaneously Diabetic HLA-A2 Transgenic NOD Mice J. Immunol., April 15, 2008; 180(8): 5430 - 5438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsui, Y. Chan, L. Tang, S. Winer, R. K. Cheung, G. Paltser, T. Selvanantham, A. R. Elford, J. R. Ellis, D. J. Becker, et al. Targeting of Pancreatic Glia in Type 1 Diabetes Diabetes, April 1, 2008; 57(4): 918 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Jarchum, J. C. Baker, T. Yamada, T. Takaki, M. P. Marron, D. V. Serreze, and T. P. DiLorenzo In Vivo Cytotoxicity of Insulin-Specific CD8+ T-Cells in HLA-A*0201 Transgenic NOD Mice Diabetes, October 1, 2007; 56(10): 2551 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Forestier, T. Takaki, A. Molano, J. S. Im, I. Baine, E. S. Jerud, P. Illarionov, R. Ndonye, A. R. Howell, P. Santamaria, et al. Improved Outcomes in NOD Mice Treated with a Novel Th2 Cytokine-Biasing NKT Cell Activator J. Immunol., February 1, 2007; 178(3): 1415 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V. Serreze, M. A. Osborne, Y.-G. Chen, H. D. Chapman, T. Pearson, M. A. Brehm, and D. L. Greiner Partial versus Full Allogeneic Hemopoietic Chimerization Is a Preferential Means to Inhibit Type 1 Diabetes as the Latter Induces Generalized Immunosuppression J. Immunol., November 15, 2006; 177(10): 6675 - 6684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takaki, M. P. Marron, C. E. Mathews, S. T. Guttmann, R. Bottino, M. Trucco, T. P. DiLorenzo, and D. V. Serreze HLA-A*0201-Restricted T Cells from Humanized NOD Mice Recognize Autoantigens of Potential Clinical Relevance to Type 1 Diabetes. J. Immunol., March 1, 2006; 176(5): 3257 - 3265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Wong, L. Li, J. A. Frelinger, and R. Tisch Early Autoimmune Destruction of Islet Grafts Is Associated with a Restricted Repertoire of IGRP-Specific CD8+ T Cells in Diabetic Nonobese Diabetic Mice J. Immunol., February 1, 2006; 176(3): 1637 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Lee, Y.-G. Chen, J. Chen, P. C. Reifsnyder, D. V. Serreze, M. Clare-Salzler, M. Rodriguez, C. Wasserfall, M. A. Atkinson, and E. H. Leiter Novel Leptin Receptor Mutation in NOD/LtJ Mice Suppresses Type 1 Diabetes Progression: II. Immunologic Analysis Diabetes, January 1, 2006; 55(1): 171 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Faideau, E. Larger, F. Lepault, J. C. Carel, and C. Boitard Role of {beta}-Cells in Type 1 Diabetes Pathogenesis Diabetes, December 1, 2005; 54(suppl_2): S87 - S96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cebecauer, P. Guillaume, P. Hozak, S. Mark, H. Everett, P. Schneider, and I. F. Luescher Soluble MHC-Peptide Complexes Induce Rapid Death of CD8+ CTL J. Immunol., June 1, 2005; 174(11): 6809 - 6819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Pomerleau, R. J. Bagley, D. V. Serreze, C. E. Mathews, and E. H. Leiter Major Histocompatibility Complex-Linked Diabetes Susceptibility in NOD/Lt Mice: Subcongenic Analysis Localizes a Component of Idd16 at the H2-D End of the Diabetogenic H2g7 Complex Diabetes, May 1, 2005; 54(5): 1603 - 1606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ejrnaes, N. Videbaek, U. Christen, A. Cooke, B. K. Michelsen, and M. von Herrath Different Diabetogenic Potential of Autoaggressive CD8+ Clones Associated with IFN-{gamma}-Inducible Protein 10 (CXC Chemokine Ligand 10) Production but Not Cytokine Expression, Cytolytic Activity, or Homing Characteristics J. Immunol., March 1, 2005; 174(5): 2746 - 2755. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
