| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
in Pancreatic Islets in the Nonobese Diabetic Mouse
Pharmacia & Upjohn, Lund Research Center, Lund, Sweden
The nonobese diabetic (NOD) mouse spontaneously develops autoimmune
insulin-dependent diabetes mellitus (IDDM) and serves as an animal
model for human type I diabetes. TNF-
is known to be produced by
islet-infiltrating mononuclear cells during insulitis and subsequent
ß cell destruction and has been implicated in the pathogenesis of
IDDM. Previously, T cells have been suggested as the main source of
TNF- in the islet infiltrate. However, on immunohistochemical
analysis of TNF- expression in islets, we are able to show that the
staining pattern of TNF- resembles that of dendritic cells (DC) and
macrophages (M
) rather than T cells and that TNF- is expressed in
islets at the very early stages of insulitis when no T cells are
detected. On double staining for TNF- and cell surface markers, we
can demonstrate that TNF- staining clearly correlates with DC and
M, whereas there is a poor correlation with T cells. This feature
was observed at both early and late stages of insulitis. TNF-
expression was also seen in NOD-SCID islets, in addition to a
peri-islet infiltration consisting of DC and M, indicating that T
cells are not required for the early DC and M infiltration and
TNF- expression in islets. In conclusion, our results show that DC
and M are the major, early source of TNF- in the NOD islet
infiltrate and that TNF- can be expressed independently of T cells,
indicating that the early DC and M infiltration and expression of
TNF- are crucial in initiation of diabetes.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 R. L. Lakey, T. G. Morgan, A. D. Rowan, J. D. Isaacs, T. E. Cawston, and C. M. U. Hilkens A novel paradigm for dendritic cells as effectors of cartilage destruction Rheumatology, May 1, 2009; 48(5): 502 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Marleau, K. L. Summers, and B. Singh Differential Contributions of APC Subsets to T Cell Activation in Nonobese Diabetic Mice J. Immunol., April 15, 2008; 180(8): 5235 - 5249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. M. Maree, M. Komba, D. T. Finegood, and L. Edelstein-Keshet A quantitative comparison of rates of phagocytosis and digestion of apoptotic cells by macrophages from normal (BALB/c) and diabetes-prone (NOD) mice J Appl Physiol, January 1, 2008; 104(1): 157 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Norris, X. Yin, M. M. Lamb, K. Barriga, J. Seifert, M. Hoffman, H. D. Orton, A. E. Baron, M. Clare-Salzler, H. P. Chase, et al. Omega-3 Polyunsaturated Fatty Acid Intake and Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes JAMA, September 26, 2007; 298(12): 1420 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Liuwantara, M. Elliot, M. W. Smith, A. O. Yam, S. N. Walters, E. Marino, A. McShea, and S. T. Grey Nuclear Factor-{kappa}B Regulates {beta}-Cell Death: A Critical Role for A20 in {beta}-Cell Protection Diabetes, September 1, 2006; 55(9): 2491 - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, Y. Liu, J. Wang, G. Ding, W. Zhang, G. Chen, M. Zhang, S. Zheng, and X. Cao Induction of Allospecific Tolerance by Immature Dendritic Cells Genetically Modified to Express Soluble TNF Receptor J. Immunol., August 15, 2006; 177(4): 2175 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F.M Maree, R. Kublik, D. T Finegood, and L. Edelstein-Keshet Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease? Phil Trans R Soc A, May 15, 2006; 364(1842): 1267 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O'Keeffe, T. C. Brodnicki, B. Fancke, D. Vremec, G. Morahan, E. Maraskovsky, R. Steptoe, L. C. Harrison, and K. Shortman Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development Int. Immunol., March 1, 2005; 17(3): 307 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hussain and T. L. Delovitch Dysregulated B7-1 and B7-2 Expression on Nonobese Diabetic Mouse B Cells Is Associated with Increased T Cell Costimulation and the Development of Insulitis J. Immunol., January 15, 2005; 174(2): 680 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guillonneau, C. Louvet, K. Renaudin, J.-M. Heslan, M. Heslan, L. Tesson, C. Vignes, C. Guillot, Y. Choi, L. A. Turka, et al. The Role of TNF-Related Activation-Induced Cytokine-Receptor Activating NF-{kappa}B Interaction in Acute Allograft Rejection and CD40L-Independent Chronic Allograft Rejection J. Immunol., February 1, 2004; 172(3): 1619 - 1629. [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]
|
|
|
|
 |
|
 M. M. W. Chong, H. E. Thomas, and T. W. H. Kay Suppressor of Cytokine Signaling-1 Regulates the Sensitivity of Pancreatic beta Cells to Tumor Necrosis Factor J. Biol. Chem., July 26, 2002; 277(31): 27945 - 27952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Prasad and C. C. Goodnow Cell-intrinsic effects of non-MHC NOD genes on dendritic cell generation in vivo Int. Immunol., June 1, 2002; 14(6): 677 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Steptoe, J. M. Ritchie, and L. C. Harrison Increased Generation of Dendritic Cells from Myeloid Progenitors in Autoimmune-Prone Nonobese Diabetic Mice J. Immunol., May 15, 2002; 168(10): 5032 - 5041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bao, Y. Yang, H.-S. Jun, and J.-W. Yoon Molecular Mechanisms for Gender Differences in Susceptibility to T Cell-Mediated Autoimmune Diabetes in Nonobese Diabetic Mice J. Immunol., May 15, 2002; 168(10): 5369 - 5375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Poligone, D. J. Weaver Jr., P. Sen, A. S. Baldwin Jr., and R. Tisch Elevated NF-{kappa}B Activation in Nonobese Diabetic Mouse Dendritic Cells Results in Enhanced APC Function J. Immunol., January 1, 2002; 168(1): 188 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Pettit, H. Weedon, M. Ahern, S. Zehntner, I. H. Frazer, J. Slavotinek, V. Au, M. D. Smith, and R. Thomas Association of clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in rheumatoid arthritis Rheumatology, November 1, 2001; 40(11): 1243 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Weaver Jr., B. Poligone, T. Bui, U. M. Abdel-Motal, A. S. Baldwin Jr., and R. Tisch Dendritic Cells from Nonobese Diabetic Mice Exhibit a Defect in NF-{kappa}B Regulation Due to a Hyperactive I{kappa}B Kinase J. Immunol., August 1, 2001; 167(3): 1461 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P.L. Chiu, D. V. Serreze, and J. S. Danska Development and Function of Diabetogenic T-cells in B-cell-Deficient Nonobese Diabetic Mice Diabetes, April 1, 2001; 50(4): 763 - 770. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Papaccio, F. Nicoletti, F. Aurelio Pisanti, K. Bendtzen, and M. galdieri Prevention of Spontaneous Autoimmune Diabetes in NOD Mice by Transferring in Vitro Antigen-Pulsed Syngeneic Dendritic Cells Endocrinology, April 1, 2000; 141(4): 1500 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hjelmstrom, J. Fjell, T. Nakagawa, R. Sacca, C. A. Cuff, and N. H. Ruddle Lymphoid Tissue Homing Chemokines Are Expressed in Chronic Inflammation Am. J. Pathol., April 1, 2000; 156(4): 1133 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dahlen, G. Hedlund, and K. Dawe Low CD86 Expression in the Nonobese Diabetic Mouse Results in the Impairment of Both T Cell Activation and CTLA-4 Up-Regulation J. Immunol., March 1, 2000; 164(5): 2444 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Green, F. S. Wong, K. Eshima, C. Mora, and R. A. Flavell Neonatal Tumor Necrosis Factor {alpha} Promotes Diabetes in Nonobese Diabetic Mice by Cd154-Independent Antigen Presentation to Cd8+ T Cells J. Exp. Med., January 17, 2000; 191(2): 225 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kagi, A. Ho, B. Odermatt, A. Zakarian, P. S. Ohashi, and T. W. Mak TNF Receptor 1-Dependent {beta} Cell Toxicity as an Effector Pathway in Autoimmune Diabetes J. Immunol., April 15, 1999; 162(8): 4598 - 4605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Bradley, V. C. Asensio, L.-K. Schioetz, J. Harbertson, T. Krahl, G. Patstone, N. Woolf, I. L. Campbell, and N. Sarvetnick Islet-Specific Th1, But Not Th2, Cells Secrete Multiple Chemokines and Promote Rapid Induction of Autoimmune Diabetes J. Immunol., March 1, 1999; 162(5): 2511 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hoglund, J. Mintern, C. Waltzinger, W. Heath, C. Benoist, and D. Mathis Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes J. Exp. Med., January 18, 1999; 189(2): 331 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Eaves, L. S. Wicker, G. Ghandour, P. A. Lyons, L. B. Peterson, J. A. Todd, and R. J. Glynne Combining Mouse Congenic Strains and Microarray Gene Expression Analyses to Study a Complex Trait: The NOD Model of Type 1 Diabetes Genome Res., February 1, 2002; 12(2): 232 - 243. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
