title: CpG promotes cross-presentation of dead cell-associated antigens by pre-CD8α+ dendritic cells [corrected].
abstract: Cross-presentation of cell-associated Ags by dendritic cells (DC) plays an important role in immunity. DC in lymphoid tissues are short lived, being continuously replaced by precursors that proliferate and differentiate locally. Paradoxically, although TLR ligands promote immune responses and stimulate DC replenishment, they impair the cross-priming capacity of terminally differentiated splenic CD8α(+) DC, the major subset involved in cross-priming. In this study, we have investigated the cross-presentation capacity of newly generated murine DC and especially immediate precursors of CD8α(+) DC. We show that these DC do not cross-present Ag from dead cells unless stimulated by TLR ligands before Ag capture. TLR ligand CpG induced the expression of costimulatory molecules required for CD8 T cell activation but also regulated the intracellular mechanisms of cross-presentation such as Ag degradation rates without regulating Ag uptake. GM-CSF, an inflammatory cytokine associated with infections, also promoted cross-presentation acquisition by pre-CD8α(+) DC and synergized with TLR9 ligand. The concept that TLR ligands as well as inflammatory cytokines promote the acquisition of cross-presenting properties by pre-CD8α(+) DC has important implications during immune responses and when considering the use of these cells for vaccination.
authors.affiliation: INSERM, U851, Lyon F-69007, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: de Brito
authors.forename: Martine
authors.initials: M
authors.lastname: Tomkowiak
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ghittoni
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Yann
authors.initials: Y
authors.lastname: Leverrier
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018899:CpG Islands / Q000502:physiology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008546:Melanoma, Experimental; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000941:Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D008024:Ligands; D008565:Membrane Proteins; D051193:Toll-Like Receptors; C084881:flt3 ligand protein