Immune Modelling & Experimental Design.
What was the challenge?
Studies in experimental immunology commonly involve complex immune pathways that cannot be tested by single or standard assays. The designing of the experiment in a model is necessary with the consideration and knowledge of multiple factors in the signalling cascade, the interaction of multiple cells and their immunogenic or tolerogenic response.
Assess if danger signals can affect the initiation of an autoimmune response.
HSC70, a chaperone was chosen as a constitutively expressed protein that acts as a danger signal. An engineered in vivo model was designed with the over expression of HSC70 in beta islet cells only, and Ag-specific CD8+ T cells. In a sterile inflammation, diabetes was induced with targetted islet beta cell damage. Incidence of diabetes was measured, and DC and T cell responses were determined to assess immune tolerance versus immune activation leading to autoimmunity.
- Initial beta cell death was responsible for the initiation of an immune mediated diabetes
- The immune response was increased by the over-expression of danger signal
- This model can be adapted into human cell based modules for translational data,
- Intervention points for treatments can be tested,
- Mechanistic data on signaling pathways for drug targeting can be generated.