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-alpha 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 NK/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 transferred with CD8+CD122+ T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.
Sato
Kengo
K
Department of Pediatrics, National Defense Medical College Tokorozawa, Saitama, Japan.
Kinoshita
Manabu
M
Motegi
Akira
A
Habu
Yoshiko
Y
Takayama
Eiji
E
Nonoyama
Shigeaki
S
Hiraide
Hoshio
H
Seki
Shuhji
S
D000367:Age Factors; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012790:Shwartzman Phenomenon / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D008070:Lipopolysaccharides; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma