Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs

Verena Semmling, Veronika Lukacs-Kornek, Christoph A Thaiss, Thomas Quast, Katharina Hochheiser, Ulf Panzer, Jamie Rossjohn, Patrick Perlmutter, Jia Cao, Dale I Godfrey, Paul B Savage, Percy A Knolle, Waldemar Kolanus, Irmgard Forster, Christian Kurts

Research output: Contribution to journalArticleResearchpeer-review

156 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)313 - 320
Number of pages8
JournalNature Immunology
Volume11
Issue number4
DOIs
Publication statusPublished - 2010

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