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

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.

Author information

1
Department of Microbiology and Immunology, Western University, London, Ontario, Canada.
2
NKT Therapeutics, Inc, Waltham, Massachusetts, USA.
3
Centre for Human Immunology, Western University, London, Ontario, Canada.
4
Lawson Health Research Institute, London, Ontario, Canada.
5
Department of Medicine, Division of Clinical Immunology and Allergy, Western University, London, Ontario, Canada.

Abstract

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

PMID:
28035011
DOI:
10.1093/infdis/jiw646
[Indexed for MEDLINE]

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