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Beta cell-specific CD80 (B7-1) expression disrupts tissue protection from autoantigen-specific CTL-mediated diabetes
Klaus Pechhold1, Wolfram Karges, Carmen Blum
1NIDDK Transplantation and Autoimmunity Branch, Bethesda, MD 20889, USA. klausp@intra.niddk.nih.gov
Journal of Autoimmunity
|February 27, 2003
Summary
Aberrant CD80 expression in pancreatic beta cells promotes autoimmune diabetes by enabling CD8 T cell infiltration. This novel mouse model aids in identifying autoantigens driving autoimmune destruction.
Area of Science:
- Immunology
- Endocrinology
- Autoimmunity
Background:
- T cell responses to pancreatic beta cell autoantigens are common but rarely cause progressive diabetes.
- Existing mouse models for diabetes often rely on spontaneous disease or high numbers of islet-specific T cells.
Purpose of the Study:
- To investigate the role of CD80 expression in pancreatic beta cells on the development of autoimmune diabetes.
- To establish a novel rodent model for studying CD8 T cell-mediated autoimmune destruction of beta cells.
Main Methods:
- Generation of RIP-CD80 transgenic mice.
- Induction of autoimmunity using lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) peptide-loaded cells.
- DNA immunization with plasmids encoding LCMV-GP or preproinsulin.
Main Results:
- RIP-CD80 mice are highly susceptible to autoantigen-induced diabetes, unlike control mice.
- CD80 expression in beta cells promotes infiltration of activated CD8 T cells, leading to insulitis and diabetes.
- DNA immunization efficiently induced diabetes in a RIP-CD80-dependent manner.
Conclusions:
- Aberrant CD80 expression in peripheral tissues abrogates natural resistance to CD8 T cell-mediated autoimmune destruction.
- This model is valuable for identifying beta cell autoantigens in autoimmune diabetes pathogenesis.
- The model serves as a prototype for uncovering autoantigens in other organ-specific autoimmune disorders.