Critical role of NK cells rather than V alpha 14(+)NKT cells in lipopolysaccharide-induced lethal shock in mice.
Although macrophages play a central role in the pathogenesis of septic shock, NK1(+) cells have also been implicated. NK1(+) cells comprise two major populations, namely NK cells and V alpha 14(+)NKT cells. To assess the relative contributions of these NK1(+) cells to LPS-induced shock, we compared the susceptibility to LPS-induced shock of beta(2)-microglobulin (beta(2)m)(-/-) mice that are devoid of V alpha 14(+)NKT cells, but not NK cells, with that of wild-type (WT) mice. The results show that beta(2)m(-/-) mice were more susceptible to LPS-induced shock than WT mice. Serum levels of IFN-gamma following LPS challenge were significantly higher in beta(2)m(-/-) mice, and endogenous IFN-gamma neutralization or in vivo depletion of NK1(+) cells rescued beta(2)m(-/-) mice from lethal effects of LPS. Intracellular cytokine staining revealed that NK cells were major IFN-gamma producers. The J alpha 281(-/-) mice that are exclusively devoid of V alpha 14(+)NKT cells were slightly more susceptible to LPS-induced shock than heterozygous littermates. Hence, LPS-induced shock can be induced in the absence of V alpha 14(+)NKT cells and IFN-gamma from NK cells is involved in this mechanism. In WT mice, hierarchic contribution of different cell populations appears likely.
Emoto
Masashi
M
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany. emoto@mpiib-berlin.mpg.de
Miyamoto
Mamiko
M
Yoshizawa
Izumi
I
Emoto
Yoshiko
Y
Schaible
Ulrich E
UE
Kita
Eiji
E
Kaufmann
Stefan H E
SH
D000818:Animals; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D012772:Shock, Septic / Q000209:etiology*; D012790:Shwartzman Phenomenon; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000502:physiology
D008070:Lipopolysaccharides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D015847:Interleukin-4; D007371:Interferon-gamma