Different subsets of natural killer T cells may vary in their roles in health and disease

Authors

  • Vipin Kumar,

    Corresponding author
    1. Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA, USA
    • Correspondence: Dr Vipin Kumar, Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.

      Email: vkumar@tpims.org

      or

      Dr Terry L. Delovitch, Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada.

      Email: del@robarts.ca

      Senior author: Vipin Kumar, Terry L. Delovitch

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  • Terry L. Delovitch

    Corresponding author
    1. Laboratory of Autoimmune Diabetes, Department of Microbiology, and Immunology, Robarts Research Institute, Western University, London, ON, Canada
    • Correspondence: Dr Vipin Kumar, Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.

      Email: vkumar@tpims.org

      or

      Dr Terry L. Delovitch, Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada.

      Email: del@robarts.ca

      Senior author: Vipin Kumar, Terry L. Delovitch

    Search for more papers by this author

Summary

Natural killer T cells (NKT) can regulate innate and adaptive immune responses. Type I and type II NKT cell subsets recognize different lipid antigens presented by CD1d, an MHC class-I-like molecule. Most type I NKT cells express a semi-invariant T-cell receptor (TCR), but a major subset of type II NKT cells reactive to a self antigen sulphatide use an oligoclonal TCR. Whereas TCR-α dominates CD1d-lipid recognition by type I NKT cells, TCR-α and TCR-β contribute equally to CD1d-lipid recognition by type II NKT cells. These variable modes of NKT cell recognition of lipid–CD1d complexes activate a host of cytokine-dependent responses that can either exacerbate or protect from disease. Recent studies of chronic inflammatory and autoimmune diseases have led to a hypothesis that: (i) although type I NKT cells can promote pathogenic and regulatory responses, they are more frequently pathogenic, and (ii) type II NKT cells are predominantly inhibitory and protective from such responses and diseases. This review focuses on a further test of this hypothesis by the use of recently developed techniques, intravital imaging and mass cytometry, to analyse the molecular and cellular dynamics of type I and type II NKT cell antigen-presenting cell motility, interaction, activation and immunoregulation that promote immune responses leading to health versus disease outcomes.

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