Related Experiment Videos
DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming
A B Bakker1, R M Hoek, A Cerwenka
1Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco 94143, USA.
Immunity
|October 6, 2000
Summary
Mice lacking DAP12 (DNAX-activating protein 12) showed resistance to experimental autoimmune encephalomyelitis. This resistance was linked to impaired T cell priming and reduced IFN-gamma production, suggesting DAP12 is crucial for immune responses.
Area of Science:
- Immunology
- Neuroimmunology
- Cellular Signaling
Background:
- DAP12 (DNAX-activating protein 12) is an ITAM-bearing adaptor protein essential for activating NK and myeloid cells.
- DAP12 deficiency in mice leads to downregulated and nonfunctional Ly49 receptors on NK cells, but seemingly normal lymphoid and myeloid development.
Purpose of the Study:
- To investigate the role of DAP12 in vivo by examining the susceptibility of DAP12-deficient (DAP12-/-) mice to experimental autoimmune encephalomyelitis (EAE).
Main Methods:
- Induction of EAE in DAP12-/- mice and wild-type littermates using myelin oligodendrocyte glycoprotein (MOG) peptide.
- Assessment of EAE susceptibility and analysis of immune cell responses, including T cell priming and cytokine production (IFN-gamma).
Main Results:
- DAP12-/- mice exhibited resistance to MOG-induced EAE.
- This resistance correlated with significantly diminished production of IFN-gamma by myelin-reactive CD4+ T cells.
- Inadequate T cell priming was observed in DAP12-deficient mice.
Conclusions:
- DAP12 signaling is essential for effective T cell priming and IFN-gamma production in the context of EAE.
- DAP12 may play a critical role in optimal antigen-presenting cell (APC) function and the inflammatory processes underlying EAE.