CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cross-presentation of exogenous antigen by plasmacytoid dendritic cells is inducible in vivo
Autor/es:
J MOURIÈS; G MORON; G SCHLECHT; G DADAGLIO; C LECLERC
Lugar:
PARÍS, FRANCIA
Reunión:
Congreso; XVI CONGRESO EUROPEO DE INMUNOLOGÍA; 2006
Resumen:
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.