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  • Review Article
  • Published:

Harnessing invariant NKT cells in vaccination strategies

Nature Reviews Immunology volume 9, pages 28–38 (2009)Cite this article

Key Points

  • Natural killer T (NKT) cells are lymphocytes that express a T-cell receptor (TCR) and markers of NK cells. Unlike conventional T cells, NKT cells recognize glycolipids that are presented in association with non-polymorphic CD1d molecules.

  • Most NKT cells (invariant NKT cells; iNKT cells) express a semi-invariant TCR α-chain: Vα14–Jα18 in mice and Vα24–Jα18 in humans. This is paired with a limited number of β-chains: Vβ11 in humans and Vβ2, Vβ7 or Vβ8 in mice.

  • iNKT cells can be activated by either endogenous glycosphingolipids or by exogenous microbial ligands. iNKT-cell activation through TCR stimulation can be enhanced by inflammatory cytokines that are secreted by antigen-presenting cells (APCs).

  • iNKT-cell activation results in TCR downregulation, proliferation and secretion of T helper 1 (TH1)- and (TH2)-type cytokines. Activated iNKT cells induce dendritic cell (DC) and B-cell maturation as well as NK-cell activation, ultimately bridging the innate and adaptive arms of the immune response.

  • iNKT cells regulate various immune responses, including tumour immunosurveillance, autoimmunity and the response to several microbial pathogens (bacteria, viruses, fungi and parasites).

  • iNKT-cell activation can be manipulated both in vitro and in vivo by using synthetic agonists (such as α-galactosylceramide) that have different binding affinities. Co-injection of iNKT-cell agonists and model antigens results in the expansion of antigen-specific B-cell and T-cell responses, and this has prompted the use of NKT-cell agonists as vaccine adjuvants in the clinical setting.

Abstract

To optimize vaccination strategies, it is important to use protocols that can 'jump-start' immune responses by harnessing cells of the innate immune system to assist the expansion of antigen-specific B and T cells. In this Review, we discuss the evidence indicating that invariant natural killer T (iNKT) cells can positively modulate dendritic cells and B cells, and that their pharmacological activation in the presence of antigenic proteins can enhance antigen-specific B- and T-cell responses. In addition, we describe structural and kinetic analyses that assist in the design of optimal iNKT-cell agonists that could be used in the clinical setting as vaccine adjuvants.

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Figure 1: Natural killer T cells interact with and modulate the function of many different cell types.
Figure 2: Examples of invariant-natural-killer-T-cell agonists.
Figure 3: Structural features of the interactions between the T-cell receptors of invariant natural killer T cells and lipid–CD1d complexes.

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Acknowledgements

We apologize to those colleagues whose data we have been unable to cite owing to space limitations. We thank A. Stock for critical reading of the manuscript.

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  1. Tumour Immunology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DU, UK

    Vincenzo Cerundolo, Jonathan D. Silk, S. Hajar Masri & Mariolina Salio

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Cerundolo, V., Silk, J., Masri, S. et al. Harnessing invariant NKT cells in vaccination strategies. Nat Rev Immunol 9, 28–38 (2009). https://doi.org/10.1038/nri2451

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