title: Langerin+ CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens.
abstract: Distinct dendritic cell (DC) subsets differ with respect to pathways of Ag uptake and intracellular routing to MHC class I or MHC class II molecules. Murine studies suggest a specialized role for CD8alpha(+) DC in cross-presentation, where exogenous Ags are presented on MHC class I molecules to CD8(+) T cells, while CD8alpha(-) DC are more likely to present extracellular Ags on MHC class II molecules to CD4(+) T cells. As a proportion of CD8alpha(+) DC have been shown to express langerin (CD207), we investigated the role of langerin(+)CD8alpha(+) DC in presenting Ag and priming T cell responses to soluble Ags. When splenic DC populations were sorted from animals administered protein i.v., the ability to cross-present Ag was restricted to the langerin(+) compartment of the CD8alpha(+) DC population. The langerin(+)CD8alpha(+) DC population was also susceptible to depletion following administration of cytochrome c, which is known to trigger apoptosis if diverted to the cytosol. Cross-priming of CTL in the presence of the adjuvant activity of the TLR2 ligand N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-Cys-[S]-Serl-[S]-Lys4-trihydrochloride or the invariant NKT cell ligand alpha-galactosylceramide was severely impaired in animals selectively depleted of langerin(+) cells in vivo. The production of IL-12p40 in response to these systemic activation stimuli was restricted to langerin(+)CD8alpha(+) DC, and the release of IL-12p70 into the serum following invariant NKT cell activation was ablated in the absence of langerin(+) cells. These data suggest a critical role for the langerin(+) compartment of the CD8alpha(+) DC population in cross-priming and IL-12 production.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Farrand
authors.forename: Nina
authors.initials: N
authors.lastname: Dickgreber
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
authors.forename: Troels R
authors.initials: TR
authors.lastname: Petersen
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002460:Cell Line; D002999:Clone Cells; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D045304:Cytochromes c / Q000008:administration & dosage / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D055879:Gene Knock-In Techniques; D006736:Horses; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055503:Protein Multimerization
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D016827:CD8 Antigens; C431698:CD8alpha antigen; D018984:Epitopes, T-Lymphocyte; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D018664:Interleukin-12; D045304:Cytochromes c