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Mice deficient in Vbeta8+NKT cells are resistant to experimental hepatitis but are partially susceptible to generalised Shwartzman reaction.
- Source :
-
Clinical and experimental medicine [Clin Exp Med] 2007 Mar; Vol. 7 (1), pp. 30-8. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Concanavalin A immunology
Concanavalin A toxicity
Galactosylceramides immunology
Galactosylceramides toxicity
Interferon-gamma blood
Interleukin-4 blood
Killer Cells, Natural drug effects
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, T-Cell, alpha-beta genetics
T-Lymphocyte Subsets drug effects
Tumor Necrosis Factor-alpha blood
Hepatitis, Animal immunology
Killer Cells, Natural immunology
Receptors, Antigen, T-Cell, alpha-beta deficiency
Shwartzman Phenomenon immunology
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1591-8890
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 17380303
- Full Text :
- https://doi.org/10.1007/s10238-007-0122-2