Send to

Choose Destination
Gastroenterology. 2011 Feb;140(2):646-55. doi: 10.1053/j.gastro.2010.10.003. Epub 2010 Oct 13.

Sulfatide-mediated activation of type II natural killer T cells prevents hepatic ischemic reperfusion injury in mice.

Author information

Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, California 92121, USA.



Hepatic ischemic reperfusion injury (IRI) is a major complication of liver transplantation and resectional hepatic surgeries. Natural killer T (NKT) cells predominate in liver, where they recognize lipid antigens bound to CD1d molecules. Type I NKT cells use a semi-invariant T-cell receptor and react with α-galactosylceramide; type II NKT cells use diverse T-cell receptors. Some type II NKT cells recognize the self-glycolipid sulfatide. It is not clear whether or how these distinct NKT cell subsets mediate hepatocellular damage after IRI.


We examined the roles of type I and type II NKT cells in mice with partial hepatic, warm ischemia, and reperfusion injury.


Mice that lack type I NKT cells (Jα18-/-) were protected from hepatic IRI, indicated by reduced hepatocellular necrosis and serum levels of alanine aminotransferase. Sulfatide-mediated activation of type II NKT cells reduced interferon-γ secretion by type I NKT cells and prevented IRI. Protection from hepatic IRI by sulfatide-mediated inactivation of type I NKT cells was associated with significant reductions in hepatic recruitment of myeloid cell subsets, especially the CD11b(+)Gr-1(int), Gr-1(-), and NK cells.


In mice, subsets of NKT cells have opposing roles in hepatic IRI: type I NKT cells promote injury whereas sulfatide-reactive type II NKT cells protect against injury. CD1d activation of NKT cells is conserved from mice to human beings, so strategies to modify these processes might be developed to treat patients with hepatic reperfusion injury.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center