This project aims at investigating the phenotype and regulation of autoreactive T cells in autoimmune diseases. In the first part of the project we will determine the frequency of autoreactive T cells and characterize their cellular phenotype in patients at disease onset. Moreover, we are investigating the impact of maternal autoimmunity on fetal immune system and on the future risk to develop organ specific autoimmune diseases. The possibility to isolate antigen−specific T cells will allow us to study the regulation of self−antigen specific T cells. Three different possibilities, not mutually exclusive, will be studied in details: a) resistance of autoreactive T cells to immune mediated suppression; b) a defective inhibitory function of T reg (decreased suppression function); c) intrinsic defect of antigen presenting cells (aberrant Ag presentation, defective costimulation).