Invariant NKT cells: regulation and function during viral infection

PLoS Pathog. 2012;8(8):e1002838. doi: 10.1371/journal.ppat.1002838. Epub 2012 Aug 16.


Natural killer T cells (NKT cells) represent a subset of T lymphocytes that express natural killer (NK) cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT), express a highly restricted T cell receptor (TCR) and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV) infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Antigens, CD1d / immunology
  • Chronic Disease
  • Immunity, Cellular*
  • Immunity, Innate*
  • Interleukins / immunology
  • Lipids / immunology
  • Mice
  • Natural Killer T-Cells / immunology*
  • Vaccination
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use
  • Virus Diseases / immunology*
  • Virus Diseases / prevention & control


  • Antigens, CD1d
  • CD1D protein, human
  • Interleukins
  • Lipids
  • Viral Vaccines
  • interleukin-22