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Clin Exp Immunol. 2014 Nov;178(2):292-309. doi: 10.1111/cei.12404.

T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis.

Author information

1
Division of General Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Abstract

Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

KEYWORDS:

Th2 response; acute intra-abdominal sepsis; glycolipids; invariant natural killer T cells

PMID:
24965554
PMCID:
PMC4233379
DOI:
10.1111/cei.12404
[Indexed for MEDLINE]
Free PMC Article

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