Insulin-dependent Diabetes Mellitus (IDDM) is an autoimmune disease which results from the selective destruction of pancreatic beta cells. Some evidences suggest that autoreactive T cells play an important role in this destruction, although the factor(s) that iniciate the disease are unknown. Diabetic patients show normal cellular responses against pathogens, but the autoimmune response has some different characteristics: autoreactive T cells are low responders but this response is maintened for years. In IDDM, endocrine cells act as antigen presenting cells since they are the specific targets of the injury and they may express molecules involved in antigen processing and presentation (MHC, B7, li, DM). However, cellular-autoantigen expression (GAD, CpH, etc) is not restricted to beta cells. In this project, we postule that the mechanism of antigen processing and presentation by epithelial cells in autoinmunity is different to antigen presenting cells, specialized in this function, and this could be tthe key for the modulation of autoinmune T cell response. For that, we propose to compare the ability of endocrine cells to present and process endogenous and exogenous autoantigen to autoreactive T cells with that of professional APC. Morphologic and functionals studies will be done to characterize the intracellular tansport and processing pathways as well as autoantigen presentation. This antigen processing and presentations study in autoinmune disease will improve the understanding of the molecular and cellular mechanisms leading to IDDM.
|Effective start/end date||7/06/96 → 7/06/99|