Most regulatory T cells CD4 + Foxp3 + ( Tregs ) are generated in the thymus. Several studies strongly suggest that the development of Tregs is due to the high affinity of their TCR for itself (complex " self peptide - MHC II ') shown in the thymus . After migrating to the periphery, Tregs continue to interact with the self and the expression of Foxp3 is considered necessary and sufficient to maintain the transcriptional program required for suppressive function of these cells in the periphery. Using two experimental models in mice, our study demonstrates the importance of ongoing interactions with itself to keep the suppressive capacity of Tregs in the periphery. The lack of interaction with the so quickly leads to an altered phenotype of Tregs , their ability to produce cytokines and also changes their transcriptional signature. Interestingly , we observed that the lack of interaction with the so does not affect the expression level of Foxp3 but self-recognition induces a unique transcriptional signature and functional characteristics that are not related to Foxp3 . In a second study, we demonstrated that in young adult mice , the expression of Ly- 6C identifies two distinct subpopulations of Tregs with phenotypic and functional differences . In particular, we observed that Tregs Ly- 6C- have a more activated phenotype and control than their counterparts Ly- 6C + and only the former are functional in vitro and in vivo. We have also shown a strong link between expression of Ly- 6C and autoreactivity , Tregs Ly- 6C- receiving over TCR signals that Ly -6C + Tregs . Finally , we observed that only Tregs Ly- 6C- remain at the periphery over time , suggesting the existence of a selection device for the preferential survival of the most functional Tregs . During my thesis, we were able to demonstrate that interactions with the self were essential and necessary for the functionality, phenotype and homeostasis of Tregs.