Mice deficient in Vβ8+NKT cells are resistant to experimental hepatitis but are partially susceptible to generalised Shwartzman reaction.

NKT cells are responsible for hepatitis induced either by concanavalin A (Con-A) or α-galactosylceramide (α-GalCer), and they are also profoundly involved in the generalised Shwartzman reaction (GSR) induced by consecutive injections of interleukin (IL)-12 and lipopolysaccharide (LPS). In the present study, using NC/Nga (NC) mice and SJL mice lacking the Vβ⁺8 gene, we examined the role of Vβ⁺8+NKT cells in hepatitis models and in the GSR. The absence of Vβ⁺8+NKT cells in the liver mononuclear cells (MNC) was confirmed by the α-GalCer/CD1d/Ig dimer. Unexpectedly, other dimer+NKT cells including Vβ7⁺NKT cells in these mice were found to decrease in comparison to that of C57BL/6 mice. No significant hepatocyte injury was observed after α-GalCer or Con-A administration in either mice. The serum interferon (IFN)-γ, IL-4 and tumour necrosis factor (TNF) levels did not increase in these mice after α-GalCer injection, however these cytokines substantially increased after Con-A administration, thus suggesting that the roles of NKT cells differ between the two hepatitis models. However, in GSR, although neither mice showed lower IFN-γ levels after a priming IL-12 injection, they showed TNF levels comparable to those in normal mice after LPS injection, and thus resulted in a decreased but substantial mortality. Although liver MNC from IL-12-injected SJL mice showed an impaired antitumour cytotoxicity, liver MNC of NC mice exhibited a greater antitumour cytotoxicity than that of C57BL/6 mice because liver NK cells proportionally increased in NC mice. These results confirm the critical role that Vβ8⁺NKT cells play in both liver and multi-organ injury. [ABSTRACT FROM AUTHOR]