| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 157, Issue 10 4726-4735, Copyright © 1996 by American Association of Immunologists
ARTICLES |
J Verdaguer, JW Yoon, B Anderson, N Averill, T Utsugi, BJ Park and P Santamaria
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Alberta, Canada.
The role of target cell autoantigens and their repertoire vs those of foreign Ags, superantigens, or non-Ag-specific stimuli in the activation and recruitment of effector T cells in most spontaneous models of autoimmune diseases remains elusive. Here we report on the use of single TCR-beta transgenic mice to study the mechanisms that drive the accumulation of pathogenic T cells in the pancreatic islets of nonobese diabetic (NOD) mice, a model for insulin-dependent diabetes mellitus. Expression of the V(beta)8.1+ TCR-beta rearrangement of a diabetogenic H-2Kd-restricted beta cell cytotoxic CD8+ T cell (beta- CTL) clone in NOD mice caused a 10-fold increase in the peripheral precursor frequency of beta-CTL and a selective acceleration of the recruitment of CD8+ T cells to the pancreatic islets of prediabetic animals. This resulted in an earlier onset and a faster progression of beta cell depletion, and led to a dramatic acceleration of the onset of diabetes. Most islet-derived beta-CTL from diabetic transgenic NOD mice expressed an endogenously-derived TCR-alpha sequence identical to that of the clonotype donating the TCR-beta transgene, and a TCR-alpha-CDR3 sequence homologous to those expressed by most islet-derived beta-CTL from nontransgenic NOD mice. TCR-beta transgene expression did not change the peripheral frequency of beta cell-specific CD4+ T cells, the rate at which these cells accumulated in the pancreatic islets, or the incidence of diabetes. Taken together, our data indicate that retention of CD8+ and CD4+ T cells in the pancreatic islets of NOD mice is driven by beta cell autoantigens, rather than by local superantigens or non-Ag- specific stimuli, and that beta-CTL are major effectors of beta cell damage in spontaneous insulin-dependent diabetes mellitus.
This article has been cited by other articles:
|
|
 |
|
  K. L. Graham, N. Sanders, Y. Tan, J. Allison, T. W. H. Kay, and B. S. Coulson Rotavirus Infection Accelerates Type 1 Diabetes in Mice with Established Insulitis J. Virol., July 1, 2008; 82(13): 6139 - 6149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Santori, Z. Popmihajlov, V. P. Badovinac, C. Smith, S. Radoja, J. T. Harty, and S. Vukmanovic TCRbeta Chain That Forms Peptide-Independent Alloreactive TCR Transfers Reduced Reactivity with Irrelevant Peptide/MHC Complex J. Immunol., May 15, 2007; 178(10): 6109 - 6114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Puertas, J. Carrillo, X. Pastor, R. M. Ampudia, A. Alba, R. Planas, R. Pujol-Borrell, M. Vives-Pi, and J. Verdaguer Phenotype and Functional Characteristics of Islet-Infiltrating B-Cells Suggest the Existence of Immune Regulatory Mechanisms in Islet Milieu Diabetes, April 1, 2007; 56(4): 940 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Meagher, G. Arreaza, A. Peters, C. A. Strathdee, P. A. Gilbert, Q.-S. Mi, P. Santamaria, G. A. Dekaban, and T. L. Delovitch CCL4 Protects From Type 1 Diabetes by Altering Islet {beta}-Cell-Targeted Inflammatory Responses Diabetes, March 1, 2007; 56(3): 809 - 817. [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]
|
|
|
|
 |
|
 J. Wang, T. Yoshida, F. Nakaki, H. Hiai, T. Okazaki, and T. Honjo Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes PNAS, August 16, 2005; 102(33): 11823 - 11828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Griseri, L. Beaudoin, J. Novak, L. T. Mars, F. Lepault, R. Liblau, and A. Lehuen Invariant NKT Cells Exacerbate Type 1 Diabetes Induced by CD8 T Cells J. Immunol., August 15, 2005; 175(4): 2091 - 2101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Qin, J. D. Trudeau, G. S. D. Reid, I-F. Lee, J. P. Dutz, P. Santamaria, C. B. Verchere, and R. Tan Progression of spontaneous autoimmune diabetes is associated with a switch in the killing mechanism used by autoreactive CTL Int. Immunol., November 1, 2004; 16(11): 1657 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Arnold, A. R. Burton, and D. A. A. Vignali Diabetes Incidence Is Unaltered in Glutamate Decarboxylase 65-Specific TCR Retrogenic Nonobese Diabetic Mice: Generation by Retroviral-Mediated Stem Cell Gene Transfer J. Immunol., September 1, 2004; 173(5): 3103 - 3111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Moore, J. Grimm, B. Han, and P. Santamaria Tracking the Recruitment of Diabetogenic CD8+ T-Cells to the Pancreas in Real Time Diabetes, June 1, 2004; 53(6): 1459 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yamanouchi, J. Verdaguer, B. Han, A. Amrani, P. Serra, and P. Santamaria Cross-Priming of Diabetogenic T Cells Dissociated from CTL-Induced Shedding of {beta} Cell Autoantigens J. Immunol., December 15, 2003; 171(12): 6900 - 6909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Martin-Orozco, Z. Chen, L. Poirot, E. Hyatt, A. Chen, O. Kanagawa, A. Sharpe, D. Mathis, and C. Benoist Paradoxical Dampening of Anti-Islet Self-Reactivity but Promotion of Diabetes by OX40 Ligand J. Immunol., December 15, 2003; 171(12): 6954 - 6960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Darwiche, M. M. W. Chong, P. Santamaria, H. E. Thomas, and T. W. H. Kay Fas Is Detectable on {beta} Cells in Accelerated, But Not Spontaneous, Diabetes in Nonobese Diabetic Mice J. Immunol., June 15, 2003; 170(12): 6292 - 6297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Serra, A. Amrani, B. Han, J. Yamanouchi, S. J. Thiessen, and P. Santamaria RAG-dependent peripheral T cell receptor diversification in CD8+ T lymphocytes PNAS, November 26, 2002; 99(24): 15566 - 15571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wen, F. S. Wong, R. Sherwin, and C. Mora Human DQ8 Can Substitute for Murine I-Ag7 in the Selection of Diabetogenic T Cells Restricted to I-Ag71 J. Immunol., April 1, 2002; 168(7): 3635 - 3640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, B. O'Brien, J. Trudeau, R. Tan, P. Santamaria, and J. P. Dutz In Situ {beta} Cell Death Promotes Priming of Diabetogenic CD8 T Lymphocytes J. Immunol., February 1, 2002; 168(3): 1466 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Viret, O. Lantz, X. He, A. Bendelac, and C. A. Janeway Jr. A NK1.1+ Thymocyte-Derived TCR {beta}-Chain Transgene Promotes Positive Selection of Thymic NK1.1+ {alpha}{beta} T Cells J. Immunol., September 15, 2000; 165(6): 3004 - 3014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Kanagawa, J. Shimizu, and B. A. Vaupel Thymic and Postthymic Regulation of Diabetogenic CD8 T Cell Development in TCR Transgenic Nonobese Diabetic (NOD) Mice J. Immunol., May 15, 2000; 164(10): 5466 - 5473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Anderson, B.-J. Park, J. Verdaguer, A. Amrani, and P. Santamaria Prevalent CD8+ T cell response against one peptide/MHC complex in autoimmune diabetes PNAS, August 3, 1999; 96(16): 9311 - 9316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Verdaguer2, A. Amrani2, B. Anderson, D. Schmidt, and P. Santamaria Two Mechanisms for the Non-MHC-Linked Resistance to Spontaneous Autoimmunity J. Immunol., April 15, 1999; 162(8): 4614 - 4626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schmidt, A. Amrani, J. Verdaguer, S. Bou, and P. Santamaria Autoantigen-Independent Deletion of Diabetogenic CD4+ Thymocytes by Protective MHC Class II Molecules J. Immunol., April 15, 1999; 162(8): 4627 - 4636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Jun, C.-S. Yoon, L. Zbytnuik, N. van Rooijen, and J.-W. Yoon The Role of Macrophages in T Cell-mediated Autoimmune Diabetes in Nonobese Diabetic Mice J. Exp. Med., January 18, 1999; 189(2): 347 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. DiLorenzo, R. T. Graser, T. Ono, G. J. Christianson, H. D. Chapman, D. C. Roopenian, S. G. Nathenson, and D. V. Serreze Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha chain gene rearrangement PNAS, October 13, 1998; 95(21): 12538 - 12543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schmidt, J. Verdaguer, N. Averill, and P. Santamaria A Mechanism for the Major Histocompatibility Complex-linked Resistance to Autoimmunity J. Exp. Med., October 6, 1997; 186(7): 1059 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yokosuka, K. Takase, M. Suzuki, Y. Nakagawa, S. Taki, H. Takahashi, T. Fujisawa, H. Arase, and T. Saito Predominant Role of T Cell Receptor (TCR)-{alpha} Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System J. Exp. Med., April 15, 2002; 195(8): 991 - 1001. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
