Main |
Browse Volumes |
Forthcoming Volumes |
Annals PrePrints |
Annals Extra |
E-mail Alerts |
Subscriptions & Orders |
New Proposals |
Author Guidelines |
About Annals |
Help |
 |
|
|
|
|
|
Beta Cell Death and Protection
THOMAS MANDRUP-POULSEN
Steno Diabetes Center, Gentofte, Denmark, and Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Address for correspondence: Thomas Mandrup-Poulsen, Steno Diabetes Center, 2 Niels Steensensvej, DK-2820 Gentofte, Denmark. Voice: +45-44-43-91-01; fax: +45-44-43-82-32.
tmpo{at}steno.dk
Ann. N.Y. Acad. Sci. 1005: 32-42 (2003).
Type 1 diabetes is an immune-mediated disease critically dependent upon the interaction between antigen-presenting cells and T cells. Clearly, both CD4+ and CD8+ T cells are required, but activated CD4+ T cells are both necessary and sufficient in causing disease. The mechanism of the Th1/Th2 immunoregulatory imbalance is unclear and needs to be further investigated. CD8+ T cells are not commonly sufficient in causing disease, but CD8 T cells are necessary in initiation (<14 weeks in the NOD mouse), but not in the later (>14 weeks) effector phase of the disease. It is still unclear whether the CD8+ T cell exerts its function as a classical effector cell or mainly as an immunomodulatory cell acting in synergy with the CD4+ T cell. The relative role of T cell effector mechanisms such as Fas/FasL, perforin/granzyme, and the TRAIL systems is unclear. Proinflammatory cytokines, reactive oxygen species, and other immune mediators seem to be involved in beta cell destruction, but much is to be learned about signaling, molecular mechanisms, and in vivo importance.
Key Words: T cell • beta cell • type 1 diabetes • tolerance • immune • signaling
This article has been cited by other articles:
|
|
|
|
 
K. L A Souza, E. Gurgul-Convey, M. Elsner, and S. Lenzen
Interaction between pro-inflammatory and anti-inflammatory cytokines in insulin-producing cells
J. Endocrinol.,
April 1, 2008;
197(1):
139 - 150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Mendes-da-Cruz, S. Smaniotto, A. C. Keller, M. Dardenne, and W. Savino
Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus
J. Immunol.,
April 1, 2008;
180(7):
4639 - 4647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cantor and K. Haskins
Recruitment and Activation of Macrophages by Pathogenic CD4 T Cells in Type 1 Diabetes: Evidence for Involvement of CCR8 and CCL1
J. Immunol.,
November 1, 2007;
179(9):
5760 - 5767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. I. Callewaert, C. A. Gysemans, L. Ladriere, W. D'Hertog, J. Hagenbrock, L. Overbergh, D. L. Eizirik, and C. Mathieu
Deletion of STAT-1 Pancreatic Islets Protects Against Streptozotocin-Induced Diabetes and Early Graft Failure but Not Against Late Rejection
Diabetes,
August 1, 2007;
56(8):
2169 - 2173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Oshima, M. M. Taketo, and M. Oshima
Destruction of Pancreatic beta-Cells by Transgenic Induction of Prostaglandin E2 in the Islets
J. Biol. Chem.,
September 29, 2006;
281(39):
29330 - 29336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kahles, E. Ramos-Lopez, B. Lange, O. Zwermann, M. Reincke, and K. Badenhoop
Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto's thyroiditis or Addison's disease in the German population
Eur. J. Endocrinol.,
December 1, 2005;
153(6):
895 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ao, N. Toy, M. K. Song, V. L. W. Go, and H. Yang
Altered Glucose and Insulin Responses to Brain Medullary Thyrotropin-Releasing Hormone (TRH)-Induced Autonomic Activation in Type 2 Diabetic Goto-Kakizaki Rats
Endocrinology,
December 1, 2005;
146(12):
5425 - 5432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Cao, J. Yang, B. R. Burkhardt, Z. Gao, R. K. Wong, S. R. Greene, J. Wu, and B. A. Wolf
Effects of overexpression of pancreatic derived factor (FAM3B) in isolated mouse islets and insulin-secreting {beta}TC3 cells
Am J Physiol Endocrinol Metab,
October 1, 2005;
289(4):
E543 - E550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Plesner, P. Liston, R. Tan, R. G. Korneluk, and C. B. Verchere
The X-Linked Inhibitor of Apoptosis Protein Enhances Survival of Murine Islet Allografts
Diabetes,
September 1, 2005;
54(9):
2533 - 2540.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Allison, H. E. Thomas, T. Catterall, T. W. H. Kay, and A. Strasser
Transgenic Expression of Dominant-Negative Fas-Associated Death Domain Protein in {beta} Cells Protects against Fas Ligand-Induced Apoptosis and Reduces Spontaneous Diabetes in Nonobese Diabetic Mice
J. Immunol.,
July 1, 2005;
175(1):
293 - 301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mukherjee, D. Wagar, T. A. Stephens, E. Lee-Chan, and B. Singh
Identification of CD4+ T Cell-Specific Epitopes of Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein: A Novel {beta} Cell Autoantigen in Type 1 Diabetes
J. Immunol.,
May 1, 2005;
174(9):
5306 - 5315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Taraseviciene-Stewart, R. Scerbavicius, K.-H. Choe, M. Moore, A. Sullivan, M. R. Nicolls, A. P. Fontenot, R. M. Tuder, and N. F. Voelkel
An Animal Model of Autoimmune Emphysema
Am. J. Respir. Crit. Care Med.,
April 1, 2005;
171(7):
734 - 742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Emanuelli, M. Glondu, C. Filloux, P. Peraldi, and E. Van Obberghen
The Potential Role of SOCS-3 in the Interleukin-1{beta}-Induced Desensitization of Insulin Signaling in Pancreatic Beta-Cells
Diabetes,
December 1, 2004;
53(suppl_3):
S97 - S103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
