| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA 19104;
Division of Nephrology, London Health Sciences Center, London, Ontaro, Canada; and
The Wistar Institute, Philadelphia, PA 19104
Diabetes in nonobese diabetic (NOD) mice results from the activation of I-Ag7-restricted, islet-reactive T cells. This study delineates several characteristics of NOD CD4 T cell activation, which, independent of I-Ag7, are likely to promote a dysregulated state of peripheral T cell tolerance. NOD CD4 T cell activation was found to be resistant to antigenic stimulation via the TCR complex, using the progression of cell division as a measure. The extent of NOD CD4 T cell division was highly sensitive to changes in Ag ligand density. Moreover, even upon maximal TCR complex-mediated stimulation, NOD CD4 T cell division prematurely terminated. Maximally stimulated NOD CD4 T cells failed to achieve the threshold number of division cycles required for optimal susceptibility to activation-induced death, a critical mechanism for the regulation of peripheral T cell tolerance. Importantly, these aberrant activation characteristics were not T cell-intrinsic but resulted from reliance on B cell costimulatory function in NOD mice. Costimulation delivered by nonautoimmune strain APCs normalized NOD CD4 T cell division and the extent of activation-induced death. Thus, by disrupting the progression of CD4 T cell division, polarization of APC costimulatory function to the B cell compartment could allow the persistence and activation of diabetogenic cells in NOD mice.
This article has been cited by other articles:
|
|
 |
|
  P. L. Kendall, D. J. Moore, C. Hulbert, K. L. Hoek, W. N. Khan, and J. W. Thomas Reduced Diabetes in btk-Deficient Nonobese Diabetic Mice and Restoration of Diabetes with Provision of an Anti-Insulin IgH Chain Transgene J. Immunol., November 15, 2009; 183(10): 6403 - 6412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Smith and T. F. Tedder Targeting B-cells Mitigates Autoimmune Diabetes in NOD Mice: What Is Plan B? Diabetes, July 1, 2009; 58(7): 1479 - 1481. [Full Text] [PDF]
|
|
|
|
|
|
G. Zekavat, S. Y. Rostami, A. Badkerhanian, R. F. Parsons, B. Koeberlein, M. Yu, C. D. Ward, T.-S. Migone, L. Yu, G. S. Eisenbarth, et al. In Vivo BLyS/BAFF Neutralization Ameliorates Islet-Directed Autoimmunity in Nonobese Diabetic Mice J. Immunol., December 1, 2008; 181(11): 8133 - 8144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Brodie, M. Wallberg, P. Santamaria, F. S. Wong, and E. A. Green B-Cells Promote Intra-Islet CD8+ Cytotoxic T-Cell Survival to Enhance Type 1 Diabetes Diabetes, April 1, 2008; 57(4): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Bour-Jordan, B. L. Salomon, H. L. Thompson, R. Santos, A. K. Abbas, and J. A. Bluestone Constitutive Expression of B7-1 on B Cells Uncovers Autoimmunity toward the B Cell Compartment in the Nonobese Diabetic Mouse J. Immunol., July 15, 2007; 179(2): 1004 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Quinn III, N. Noorchashm, J. E. Crowley, A. J. Reed, H. Noorchashm, A. Naji, and M. P. Cancro Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse. J. Immunol., June 15, 2006; 176(12): 7159 - 7164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Moore, H. Noorchashm, T. H. Lin, S. A. Greeley, and A. Naji NOD B-cells Are Insufficient to Incite T-Cell-Mediated Anti-islet Autoimmunity Diabetes, July 1, 2005; 54(7): 2019 - 2025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sblattero, F. Maurano, G. Mazzarella, M. Rossi, S. Auricchio, F. Florian, F. Ziberna, A. Tommasini, T. Not, A. Ventura, et al. Characterization of the Anti-Tissue Transglutaminase Antibody Response in Nonobese Diabetic Mice J. Immunol., May 1, 2005; 174(9): 5830 - 5836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Acevedo-Suarez, C. Hulbert, E. J. Woodward, and J. W. Thomas Uncoupling of Anergy from Developmental Arrest in Anti-Insulin B Cells Supports the Development of Autoimmune Diabetes J. Immunol., January 15, 2005; 174(2): 827 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Vence, C. Benoist, and D. Mathis Fas Deficiency Prevents Type 1 Diabetes by Inducing Hyporesponsiveness in Islet {beta}-Cell-Reactive T-Cells Diabetes, November 1, 2004; 53(11): 2797 - 2803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hussain, K. V. Salojin, and T. L. Delovitch Hyperresponsiveness, Resistance to B-Cell Receptor--Dependent Activation-Induced Cell Death, and Accumulation of Hyperactivated B-Cells in Islets Is Associated With the Onset of Insulitis but not Type 1 Diabetes Diabetes, August 1, 2004; 53(8): 2003 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Silveira, J. Dombrowsky, E. Johnson, H. D. Chapman, D. Nemazee, and D. V. Serreze B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice J. Immunol., April 15, 2004; 172(8): 5086 - 5094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Makhlouf, A. Yamada, T. Ito, R. Abdi, M. J. I. Ansari, C. Q. Khuong, H. J. Winn, H. Auchincloss Jr., and M. H. Sayegh Allorecognition and Effector Pathways of Islet Allograft Rejection in Normal versus Nonobese Diabetic Mice J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2168 - 2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chen, W.-H. Lee, P. Yun, P. Snow, and C.-P. Liu Induction of Autoantigen-Specific Th2 and Tr1 Regulatory T Cells and Modulation of Autoimmune Diabetes J. Immunol., July 15, 2003; 171(2): 733 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Bergman, N. Duarte, S. Campino, M. Lundholm, V. Motta, K. Lejon, C. Penha-Goncalves, and D. Holmberg Diabetes Protection and Restoration of Thymocyte Apoptosis in NOD Idd6 Congenic Strains Diabetes, July 1, 2003; 52(7): 1677 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pearson, T. G. Markees, D. V. Serreze, M. A. Pierce, M. P. Marron, L. S. Wicker, L. B. Peterson, L. D. Shultz, J. P. Mordes, A. A. Rossini, et al. Genetic Disassociation of Autoimmunity and Resistance to Costimulation Blockade-Induced Transplantation Tolerance in Nonobese Diabetic Mice J. Immunol., July 1, 2003; 171(1): 185 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sen, S. Bhattacharyya, M. Wallet, C. P. Wong, B. Poligone, M. Sen, A. S. Baldwin Jr., and R. Tisch NF-{kappa}B Hyperactivation Has Differential Effects on the APC Function of Nonobese Diabetic Mouse Macrophages J. Immunol., February 15, 2003; 170(4): 1770 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. L. Chiu, A. M. Jevnikar, and J. S. Danska Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice J. Immunol., December 15, 2001; 167(12): 7169 - 7179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. W. Greeley, D. J. Moore, H. Noorchashm, L. E. Noto, S. Y. Rostami, A. Schlachterman, H. K. Song, B. Koeberlein, C. F. Barker, and A. Naji Impaired Activation of Islet-Reactive CD4 T Cells in Pancreatic Lymph Nodes of B Cell-Deficient Nonobese Diabetic Mice J. Immunol., October 15, 2001; 167(8): 4351 - 4357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Johnson, P. Silveira, H. D. Chapman, E. H. Leiter, and D. V. Serreze Inhibition of Autoimmune Diabetes in Nonobese Diabetic Mice by Transgenic Restoration of H2-E MHC Class II Expression: Additive, But Unequal, Involvement of Multiple APC Subtypes J. Immunol., August 15, 2001; 167(4): 2404 - 2410. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
