title: Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs.
abstract: Cross-priming allows dendritic cells (DCs) to induce cytotoxic T cell (CTL) responses to extracellular antigens. DCs require cognate 'licensing' for cross-priming, classically by helper T cells. Here we demonstrate an alternative mechanism for cognate licensing by natural killer T (NKT) cells recognizing microbial or synthetic glycolipid antigens. Such licensing caused cross-priming CD8alpha(+) DCs to produce the chemokine CCL17, which attracted naive CTLs expressing the chemokine receptor CCR4. In contrast, DCs licensed by helper T cells recruited CTLs using CCR5 ligands. Thus, depending on the type of antigen they encounter, DCs can be licensed for cross-priming by NKT cells or helper T cells and use at least two independent chemokine pathways to attract naive CTLs. Because these chemokines acted synergistically, this can potentially be exploited to improve vaccinations.
authors.affiliation: Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, Bonn, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Semmling
authors.forename: Veronika
authors.initials: V
authors.lastname: Lukacs-Kornek
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Quast
authors.forename: Katharina
authors.initials: K
authors.lastname: Hochheiser
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Patrick
authors.initials: P
authors.lastname: Perlmutter
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002469:Cell Separation; D054414:Chemokine CCL17 / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D054398:Receptors, CCR4 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D054398:Receptors, CCR4