Abstract
The mechanism by which β-cells die during autoimmune diabetes has remained a subject of intense investigation. The loss of β-cells in the disease is T cell mediated and thought to result from a number of different insults including apoptosis induction through the death receptor CD95. However, the role of CD95 in autoimmune diabetes, studied primarily in the non-obese diabetic (NOD) mouse model, has been controversial. We have used an alternative model of autoimmune diabetes triggered by repeated low doses of streptozotocin. In this model, islet grafts from C3H mice that carry the lpr mutation, and therefore lack the ability to undergo apoptosis through CD95-CD95L interaction, were completely protected when grafted in autoimmune diabetic mice despite periinsulitis (infiltration of T cells) which however did not progress to islet destruction. In contrast wild-type grafts were rapidly eliminated in autoimmune recipients. Our data provide strong support for a major role of CD95 in the destruction of islets in autoimmune mice.
Original language | English (US) |
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Pages (from-to) | 725-730 |
Number of pages | 6 |
Journal | Apoptosis |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2005 |
Funding
We would like to thank Dr. L. Philipson for help with the isolation of islets. This work was funded by NIH grant R21 AI55465.
Keywords
- Apoptosis
- CD95
- Type I diabetes
- lpr
ASJC Scopus subject areas
- Biochemistry, medical
- Cancer Research
- Clinical Biochemistry
- Cell Biology
- Pharmacology
- Pharmaceutical Science