| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
National Institute of Diabetes and Digestive and Kidney Diseases-Navy Transplantation and Autoimmunity Branch, Bethesda, MD 20889; and
Department of Internal Medicine I, University of Ulm, Ulm, Germany
Although transgenic mice expressing murine B7-1 (mCD80) on their
pancreatic 
cells under the rat insulin-1 promoter
(RIP-mCD80+ mice) rarely develop spontaneous cell
destruction and diabetes, we have previously reported the
transgene-dependent induction of profound insulitis and lethal diabetes
following multiple low dose injections of the cell toxin
streptozotocin (MLDS) in RIP-mCD80+ mice. Here, we have
further characterized this MLDS-induced diabetes model using the
RIP-mCD80+ mice and now demonstrate that disease is
critically dependent on T cell signaling via CD28. Thus, although naive
RIP-mCD80+ and nontransgenic littermates have comparable
gross cell mass, and immediately following MLDS induction the mice
display similar degrees of insulitis and decrements in the cell
mass, only transgenic mice continued to destroy their cells and
develop insulin-dependent diabetes mellitus. Strikingly, MLDS-induced
diabetes was completely prevented in CD28-deficient mice
(RIP-mCD80+CD28-/-) due to abrogation of
leukocytes infiltrating their pancreatic islets. We further
characterized MLDS-induced diabetes in the RIP-mCD80+ mice
by demonstrating that the MLDS-induced lymphocytic islet infiltrate
contained a substantial frequency of autoantigen-specific,
IFN-
-secreting, CD8+ T cells. We conclude that
MLDS-induced cell destruction and subsequent insulin-dependent
diabetes mellitus in RIP-mCD80+ mice is T cell-mediated as
it involves both Ag-specific recognition of self-target molecules in
the inflamed pancreatic islet (signal 1) and is CD28 costimulation
dependent (signal 2).
This article has been cited by other articles:
|
|
 |
|
  C. C. Chuang, R. S. Yang, K. S. Tsai, F. M. Ho, and S. H. Liu Hyperglycemia Enhances Adipogenic Induction of Lipid Accumulation: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2, Phosphoinositide 3-Kinase/Akt, and Peroxisome Proliferator-Activated Receptor {gamma} Signaling Endocrinology, September 1, 2007; 148(9): 4267 - 4275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Botolin and L. R. McCabe Bone Loss and Increased Bone Adiposity in Spontaneous and Pharmacologically Induced Diabetic Mice Endocrinology, January 1, 2007; 148(1): 198 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Botolin, M.-C. Faugere, H. Malluche, M. Orth, R. Meyer, and L. R. McCabe Increased Bone Adiposity and Peroxisomal Proliferator-Activated Receptor-{gamma}2 Expression in Type I Diabetic Mice Endocrinology, August 1, 2005; 146(8): 3622 - 3631. [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]
|
|
|
|
 |
|
 W. Karges, K. Pechhold, S. Al Dahouk, I. Riegger, M. Rief, A. Wissmann, R. Schirmbeck, C. Barth, and B. O. Boehm Induction of Autoimmune Diabetes Through Insulin (but Not GAD65) DNA Vaccination in Nonobese Diabetic and in RIP-B7.1 Mice Diabetes, November 1, 2002; 51(11): 3237 - 3244. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
