NKT cells: the culprits of sepsis?

Department of Surgery, University of California, San Francisco, California 94143-0104, USA.
Journal of Surgical Research (Impact Factor: 2.12). 10/2010; 167(1):87-95. DOI: 10.1016/j.jss.2010.09.038
Source: PubMed

ABSTRACT Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex pro-inflammatory cascades that include the activation of various immune cells and the exuberant secretion of pro-inflammatory cytokines by these cells. Natural killer T-cells (NKT) are a sub-lineage of T cells that share characteristics of conventional T cells and NK cells, and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation.

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    ABSTRACT: NK1.1+ natural killer (NK)-T cells reactive to CD1 appear to be involved in spontaneous autoimmune disease, but their role in induced autoimmune disease remains unclear. While we previously reported a regulatory role of NK cells in experimental autoimmune encephalomyelitis (EAE), we demonstrate here that NK-T cells would also play a pivotal role in the control of EAE. C57BL/6 (B6) mice selectively depleted for NK-T cells were generated by antibody-depended protocols or knocking out TCRJα281 gene. Regardless of the method for NK-T cell deletion, these NK-T depleted mice developed unusually early onset of EAE (5–8 days after challenge) after immunization with an encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)35–55. The early EAE onset was associated with early induction of T helper cell type 1 (Th1) cells and marked elevation of Th1 cytokines in the serum. It was of note that, although the NK-T deficient mice spontaneously recovered from EAE, mice selectively depleted for NK cells developed a later onset of non-remitting EAE. These data establish differential roles played by NK-T and NK cells in the protection against EAE.
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    ABSTRACT: Natural killer T (NKT) lymphocytes are implicated in the early response to microbial infection. Further, sulfatide, a myelin self-glycosphingolipid, activates a type II NKT cell subset, and can modulate disease in murine models. We examined the role of NKT cells and the effect of sulfatide treatment in a murine model of Staphylococcus aureus sepsis. Lack of CD1d-restricted NKT cells did not alter survival after a lethal inoculum of S. aureus. In contrast, sulfatide treatment significantly improved the survival rate of mice with S. aureus sepsis, accompanied by decreased levels of TNF-α and IL-6 in the blood. The protective effect of sulfatide treatment depended on CD1d, but not on type I NKT cells, suggesting that activation of type II NKT cells by sulfatide has beneficial effects on the outcome of S. aureus sepsis in this model.
    Infection and immunity 01/2013; DOI:10.1128/IAI.01334-12 · 4.16 Impact Factor

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