TY - JOUR
T1 - Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs
AU - Semmling, Verena
AU - Lukacs-Kornek, Veronika
AU - Thaiss, Christoph A.
AU - Quast, Thomas
AU - Hochheiser, Katharina
AU - Panzer, Ulf
AU - Rossjohn, Jamie
AU - Perlmutter, Patrick
AU - Cao, Jia
AU - Godfrey, Dale I.
AU - Savage, Paul B.
AU - Knolle, Percy A.
AU - Kolanus, Waldemar
AU - Förster, Irmgard
AU - Kurts, Christian
N1 - Funding Information:
We thank W. Keßler (University of Greifswald) for CCR4-deficient mice; F. Tacke (University of Aachen) for CD1dand MHC class II–deficient mice; R. Goldszmid (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for CD8-deficient mice; J. Alferink (University of Bonn) for CCL17-eGFP knock-in mice; A. Peters for technical assistance; C. Coch and Rolf Fimmers for advice on statistics; and the Central Animal Facilities and the Flow Cytometry Core Facility at the Institutes of Molecular Medicine and Experimental Immunology for support. Supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 704 grants A1 (I.F.),A2 (C.K.),A5 (P.A.K.) and A8 (W.K.), and Klinische Forschergruppe 228 grants P1 (U.P.) and P5 (C.K.)), the Australian National Health and Medical Research Council (D.I.G. and J.R.) and the Australian Research Council (J.R.).
PY - 2010
Y1 - 2010
N2 - 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 CD8α+ 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.
AB - 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 CD8α+ 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.
UR - http://www.scopus.com/inward/record.url?scp=77949830320&partnerID=8YFLogxK
U2 - 10.1038/ni.1848
DO - 10.1038/ni.1848
M3 - Article
C2 - 20190758
AN - SCOPUS:77949830320
SN - 1529-2908
VL - 11
SP - 313
EP - 320
JO - Nature Immunology
JF - Nature Immunology
IS - 4
ER -
