Mice deficient in Vbeta8+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 alpha-galactosylceramide (alpha-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 Vbeta(+)8 gene, we examined the role of Vbeta(+)8+NKT cells in hepatitis models and in the GSR. The absence of Vbeta(+)8+NKT cells in the liver mononuclear cells (MNC) was confirmed by the alpha-GalCer/CD1d/Ig dimer. Unexpectedly, other dimer+NKT cells including Vbeta7(+)NKT cells in these mice were found to decrease in comparison to that of C57BL/6 mice. No significant hepatocyte injury was observed after alpha-GalCer or Con-A administration in either mice. The serum interferon (IFN)-gamma, IL-4 and tumour necrosis factor (TNF) levels did not increase in these mice after alpha-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-gamma 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 Vbeta8(+)NKT cells play in both liver and multi-organ injury.
Habu
Y
Y
Department of Immunology and Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan,.
Shinomiya
N
N
Kinoshita
M
M
Matsumoto
A
A
Kawabata
T
T
Seki
S
S
D000818:Animals; D003208:Concanavalin A / Q000276:immunology / Q000633:toxicity; D005699:Galactosylceramides / Q000276:immunology / Q000633:toxicity; D006520:Hepatitis, Animal / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D012790:Shwartzman Phenomenon / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C075784:T cell receptor Vbeta8; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma