When DCs are not directly infected, a unique pathway called cross-presentation allows them to

initiate CD8+ T cell responses by cross-priming. Cross-priming is a crucial mechanism by which

internalized exogenous Ags are delivered into the MHC-I pathway in order to activate CD8+ T

cells. Plasmacytoid dendritic cells (pDCs) represent a subset of DCs characterized by their

ability to produce high amount of IFN-± during viral infection. Since pDCs play a central role in

viral immunity, we wondered whether pDCs were able to capture and cross-present exogenous

Ag to CD8+ T cells. We show that splenic and bone marrow (BM)-derived pDCs efficiently

capture and degrade Ags, but only BM-derived pDCs are able to cross-present Ags

constitutively. Moreover, we establish that in vitro TLR-7 or TLR-9 stimulation allows pDCs to

cross-present Ags to a MHC-I restricted T cell hybridoma. In addition, in vivo TLR-7 or TLR-9

stimulation or viral activation together with Ag delivery licenses pDCs to cross-prime naive

CD8+ T cells that fully differentiate into effector cells. Nevertheless, if TLR stimulation happens

before Ag encounter, cross-presentation is inhibited, while capture and degradation ability

remains efficient. This study demonstrates that pDC cross-presentation capacity is tightly

regulated and can be either induced or inhibited following activation by TLR-7 or 9 ligands.

Moreover, these findings highlight the role of pDCs in adaptive immunity showing that pDCs

could be involved in the induction of anti-viral responses.