Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice

We examined the role of mouse CD8(+) CD122(+) T cells, which increase in number with age, in the generalized Shwartzman reaction. This reaction was induced by IL-12 priming and subsequent LPS challenge (after 24 h) in mice of various ages (4-50 weeks of age). Although most young mice (4 or 6 weeks of age) survived, mortality essentially increased with increasing age of the mice, and all mice of 20 weeks of age or older died within 48 h. Serum TNF-alpha, levels after LPS challenge also increased age dependently. The neutralization of either IL-12-induced IFN-gamma or LPS-induced TNF-alpha improved the survival of middle-aged (25-week-old) mice. Both IFN-gamma production after IL-12 priming and TNF-a. production from the liver mononuclear cells after LPS challenge were also prominent in the middle-aged mice. CD8(+) CD122(+) T cells cultured with IL-12 produced a much larger amount of IFN-gamma than CD8(+)CD122(-) T cells. Although the depletion of NY/NK T cells did not decrease the IFN-gamma or TNF-alpha production in the Shwartzman reaction of the middle-aged mice, an additional depletion of CD8(+)CD122(+) T cells did decrease such production and also improved mouse survival. Furthermore, young mice T lymphocytes transferred with CD8(+)CD122(+) T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.