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Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming

Nature Immunology volume 5, pages 1260–1265 (2004)Cite this article

Abstract

Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (TH1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-γ (IFN-γ) that is necessary for TH1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate TH1 responses.

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Figure 1: NK cells are recruited and activated in DC-draining lymph nodes.
Figure 2: NK cells reach DC-draining lymph nodes in a CCR7-independent, CXCR3-dependent fashion.
Figure 3: Adjuvants that recruit NK cells induce TH1 polarization.
Figure 4: In vivo depletion of NK cells leads to defective TH1 polarization.
Figure 5: IFN-γ produced by migrating NK cells is necessary for TH1 polarization.

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Acknowledgements

We thank M. Uguccioni for reading the manuscript and for comments. This work was supported by grants from the Swiss National Science Foundation (31-63885) and from the European Commission ('Memovax' QLK2-CT-2001-01205 and 'Main' FP6-502935). The Institute for Research in Biomedicine is supported by the Helmut Horten Foundation.

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Authors and Affiliations

  1. Institute for Research in Biomedicine, Bellinzona, 6500, Switzerland

    Alfonso Martín-Fontecha, Antonio Lanzavecchia & Federica Sallusto

  2. Glaxo Smith and Kline, Stevenage, SG12NY, Herts, UK

    Lindy L Thomsen & Sara Brett

  3. Perlmutter Laboratory, Children's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Craig Gerard

  4. Max Delbrück Center for Molecular Medicine, Berlin-Buch, 13092, Germany

    Martin Lipp

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  1. Alfonso Martín-Fontecha
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Correspondence to Alfonso Martín-Fontecha or Federica Sallusto.

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Supplementary information

Supplementary Fig. 1

Kinetics of NK cell migration to lymph nodes. (PDF 62 kb)

Supplementary Fig. 2

Injection in vivo of anti-asialo GM-1 antibody results in the depletion of NK cells but not of αβ T cells, γδ T cells, or B cells. (PDF 116 kb)

Supplementary Fig. 3

Purity of NK cells used for transfer and migration experiments. (PDF 43 kb)

Supplementary Fig. 4

B6D2F1 mice were adoptively transferred with DO11.10 T cells and depleted of NK cells by injection of anti-NK1.1 antibody. (PDF 74 kb)

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Martín-Fontecha, A., Thomsen, L., Brett, S. et al. Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming. Nat Immunol 5, 1260–1265 (2004). https://doi.org/10.1038/ni1138

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