Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs.
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.
Semmling
Verena
V
Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, Bonn, Germany.
Lukacs-Kornek
Veronika
V
Thaiss
Christoph A
CA
Quast
Thomas
T
Hochheiser
Katharina
K
Panzer
Ulf
U
Rossjohn
Jamie
J
Perlmutter
Patrick
P
Cao
Jia
J
Godfrey
Dale I
DI
Savage
Paul B
PB
Knolle
Percy A
PA
Kolanus
Waldemar
W
Förster
Irmgard
I
Kurts
Christian
C
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
C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D054398:Receptors, CCR4