Immunological tolerance to self is essential in the prevention of autoimmune disease. The two main types of DCs, conventional DC (cDCs) and plasmacytoid DC (pDCs), are involved in peripheral tolerance induction. Recently, LN resident radio-resistant cells, the LN stromal cells (LNSCs), have been suggested to contribute to peripheral T cell tolerance. Here we show that LNSCs contribute to CD4+ T cell tolerance via the acquisition of peptide-MHCII complexes from DCs. Moreover, we also explored a therapeutic role for pDCs in a mouse model of Multiple Sclerosis, the experimental autoimmune encephalomyelitis (EAE). Adoptive transfer of pDCs into C57BL/6 mice after EAE onset induced significant inhibition of EAE clinical symptoms. The elucidation of the cellular and molecular mechanisms involved in pDC-mediated EAE inhibition could shed light into an important therapeutic role for pDCs in MS. In conclusion, my work unraveled some important cellular and molecular mechanisms that underpin the tolerizing roles of Ag presentation by new cell types, from both the hematopoietic and the nonhematopoietic origins.