Invariant Natural Killer T Cells Are Pathogenic in the HLA-DR4-Transgenic Humanized Mouse Model of Toxic Shock Syndrome and Can Be Targeted to Reduce Morbidity

J Infect Dis. 2017 Mar 1;215(5):824-829. doi: 10.1093/infdis/jiw646.


During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T -cell response leading to a potentially catastrophic "cytokine storm". Whether innate-like invariant natural killer T (iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B (SEB). Both approaches indicate that iNKT cells are pathogenic in TSS. Importantly, treating DR4tg mice with a TH2-polarizing glycolipid agonist of iNKT cells reduced SEB-inflicted morbidity/mortality. Therefore, iNKT cells may constitute an attractive therapeutic target in superantigen-mediated illnesses.

Keywords: Invariant natural killer T cells; Staphylococcus aureus; inflammation; staphylococcal enterotoxin B; superantigen; toxic shock syndrome; cytokines.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enterotoxins / immunology
  • HLA-DR4 Antigen / genetics*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology*
  • Shock, Septic / immunology*
  • Shock, Septic / prevention & control*
  • Superantigens / blood
  • Superantigens / immunology


  • Enterotoxins
  • HLA-DR4 Antigen
  • Superantigens
  • enterotoxin B, staphylococcal