| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Cell Death Promotes Priming of Diabetogenic CD8 T Lymphocytes1
,
Departments of
*
Medicine and
Pathology and Laboratory Medicine, British Columbia Research Institute of Children and Women’s Health, University of British Columbia, Vancouver, British Columbia, Canada;
Department of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; and
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
CTLs are important mediators of pancreatic 
cell destruction in
the nonobese diabetic mouse model of type 1 diabetes.
Cross-presentation of Ag is one means of priming CTLs. The death of
Ag-bearing cells has been implicated in facilitating this mode of
priming. The role of cell death in facilitating the onset of
spontaneous autoimmune diabetes is unknown. Here, we used an adoptive
transfer system to determine the time course of islet-derived Ag
presentation to naive cell-specific CD8 T cells in nonobese
diabetic mice and to test the hypothesis that cell death enhances
the presentation of cell autoantigen. We have determined that
cell death enhances autoantigen presentation. Priming of diabetogenic
CD8 T cells in the pancreatic lymph nodes was negligible before 4 wk,
progressively increased until 8 wk of age, and was not influenced by
gender. Administration of multiple low doses of the cell toxin
streptozotocin augmented in situ cell apoptosis and accelerated the
onset and magnitude of autoantigen presentation to naive CD8 T cells.
Increasing doses of streptozotocin resulted in both increased
pancreatic cell death and significantly enhanced T cell priming.
These results indicate that in situ cell death facilitates
autoantigen-specific CD8 T cell priming and can contribute to both the
initiation and the ongoing amplification of an autoimmune
response.
This article has been cited by other articles:
|
|
 |
|
  M.-u. Alam, J. A. Harken, A.-M. Knorn, A. R. Elford, K. Wigmore, P. S. Ohashi, and D. G. Millar Transgenic Expression of Hsc70 in Pancreatic Islets Enhances Autoimmune Diabetes in Response to {beta} Cell Damage J. Immunol., November 1, 2009; 183(9): 5728 - 5737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P.R. Sutherland, T. Van Belle, A. L. Wurster, A. Suto, M. Michaud, D. Zhang, M. J. Grusby, and M. von Herrath Interleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Mice Diabetes, May 1, 2009; 58(5): 1144 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Wong, L. Khai Siew, G. Scott, I. J. Thomas, S. Chapman, C. Viret, and L. Wen Activation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes Diabetes, May 1, 2009; 58(5): 1156 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, S. Cho, A. Ueno, L. Cheng, B.-Y. Xu, M. D. Desrosiers, Y. Shi, and Y. Yang Ligand-Dependent Induction of Noninflammatory Dendritic Cells by Anergic Invariant NKT Cells Minimizes Autoimmune Inflammation J. Immunol., August 15, 2008; 181(4): 2438 - 2445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Calderon, A. Suri, M. J. Miller, and E. R. Unanue Dendritic cells in islets of Langerhans constitutively present {beta} cell-derived peptides bound to their class II MHC molecules PNAS, April 22, 2008; 105(16): 6121 - 6126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Martin, M. G. Grisotto, C. Canasto-Chibuque, S. L. Kunkel, J. S. Bromberg, G. C. Furtado, and S. A. Lira Islet Expression of M3 Uncovers a Key Role for Chemokines in the Development and Recruitment of Diabetogenic Cells in NOD Mice Diabetes, February 1, 2008; 57(2): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ueno, S. Cho, L. Cheng, J. Wang, S. Hou, H. Nakano, P. Santamaria, and Y. Yang Transient Upregulation of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Human Chorionic Gonadotropin Downregulates Autoimmune Diabetes Diabetes, June 1, 2007; 56(6): 1686 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Dudek, H. E. Thomas, L. Mariana, R. M. Sutherland, J. Allison, E. Estella, E. Angstetra, J. A. Trapani, P. Santamaria, A. M. Lew, et al. Cytotoxic T-Cells From T-Cell Receptor Transgenic NOD8.3 Mice Destroy {beta}-Cells via the Perforin and Fas Pathways Diabetes, September 1, 2006; 55(9): 2412 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. M. Maree, P. Santamaria, and L. Edelstein-Keshet Modeling competition among autoreactive CD8+ T cells in autoimmune diabetes: implications for antigen-specific therapy Int. Immunol., July 1, 2006; 18(7): 1067 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishimaru, R. Arakaki, F. Omotehara, K. Yamada, K. Mishima, I. Saito, and Y. Hayashi Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands Mol. Cell. Biol., April 15, 2006; 26(8): 2924 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Peng, H. Shao, Y. Ke, P. Zhang, J. Xiang, H. J. Kaplan, and D. Sun In Vitro Activation of CD8 Interphotoreceptor Retinoid-Binding Protein-Specific T Cells Requires not only Antigenic Stimulation but also Exogenous Growth Factors. J. Immunol., April 15, 2006; 176(8): 5006 - 5014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Martinez, H. T. C. Kreuwel, W. L. Redmond, R. Trenney, K. Hunter, H. Rosen, N. Sarvetnick, L. S. Wicker, and L. A. Sherman CD8+ T Cell Tolerance in Nonobese Diabetic Mice Is Restored by Insulin-Dependent Diabetes Resistance Alleles J. Immunol., August 1, 2005; 175(3): 1677 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jorns, A. Gunther, H.-J. Hedrich, D. Wedekind, M. Tiedge, and S. Lenzen Immune Cell Infiltration, Cytokine Expression, and {beta}-Cell Apoptosis During the Development of Type 1 Diabetes in the Spontaneously Diabetic LEW.1AR1/Ztm-iddm Rat Diabetes, July 1, 2005; 54(7): 2041 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Medarova, S. Bonner-Weir, M. Lipes, and A. Moore Imaging {beta}-Cell Death With a Near-Infrared Probe Diabetes, June 1, 2005; 54(6): 1780 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Liadis, K. Murakami, M. Eweida, A. R. Elford, L. Sheu, H. Y. Gaisano, R. Hakem, P. S. Ohashi, and M. Woo Caspase-3-Dependent {beta}-Cell Apoptosis in the Initiation of Autoimmune Diabetes Mellitus Mol. Cell. Biol., May 1, 2005; 25(9): 3620 - 3629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lieberman, T. Takaki, B. Han, P. Santamaria, D. V. Serreze, and T. P. DiLorenzo Individual Nonobese Diabetic Mice Exhibit Unique Patterns of CD8+ T Cell Reactivity to Three Islet Antigens, Including the Newly Identified Widely Expressed Dystrophia Myotonica Kinase J. Immunol., December 1, 2004; 173(11): 6727 - 6734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Flodstrom-Tullberg, D. Yadav, R. Hagerkvist, D. Tsai, P. Secrest, A. Stotland, and N. Sarvetnick Target Cell Expression of Suppressor of Cytokine Signaling-1 Prevents Diabetes in the NOD Mouse Diabetes, November 1, 2003; 52(11): 2696 - 2700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rajagopalan, Y. C. Kudva, L. Chen, L. Wen, and C. S. David Autoimmune diabetes in HLA-DR3/DQ8 transgenic mice expressing the co-stimulatory molecule B7-1 in the {beta} cells of islets of Langerhans Int. Immunol., September 1, 2003; 15(9): 1035 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rajagopalan, Y. C. Kudva, R. A. Flavell, and C. S. David Accelerated Diabetes in Rat Insulin Promoter-Tumor Necrosis Factor-{alpha} Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules Diabetes, February 1, 2003; 52(2): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Ichikawa, L. P. Williams, and B. M. Segal Activation of APCs Through CD40 or Toll-Like Receptor 9 Overcomes Tolerance and Precipitates Autoimmune Disease J. Immunol., September 1, 2002; 169(5): 2781 - 2787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Gagnerault, J. J. Luan, C. Lotton, and F. Lepault Pancreatic Lymph Nodes Are Required for Priming of {beta} Cell Reactive T Cells in NOD Mice J. Exp. Med., August 5, 2002; 196(3): 369 - 377. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
