We have shown that IFN-I promotes development of human type 1 regulatory-like cells (Tr1) that produce the anti-inflammatory cytokine IL-10, and have studied the integration of T cell receptor (TCR) signal strength and CD28 costimulation in this process. Tr1 cells can dampen the immune response and contribute to tolerance in clinical transplantation. However, these cells represent an heterogeneous population, whose induction and phenotypic and functional properties remain to be studied. Ongoing investigations aim at deciphering the molecular mechanisms involved in the cooperation between TCR and IFN-I towards IL-10 expression and development of Tr1 cells. Notably, we study the integration of TCR and IFN-I signaling pathways, transcriptional regulation of cytokine expression and we perform large scale transcriptomic analyses.