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

Abstract

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‐α levels after LPS challenge also increased age dependently. The neutralization of either IL‐12‐induced IFN‐γ or LPS‐induced TNF‐α improved the survival of middle‐aged (25‐week‐old) mice. Both IFN‐γ production after IL‐12 priming and TNF‐α 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‐γ than CD8+CD122– T cells. Although the depletion of NK/NK T cells did not decrease the IFN‐γ or TNF‐α 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.

CD8+ CD122+ PD-1− effector cells promote the development of diabetes in NOD mice

“…In agreement with other publications, we observed that CD8 + CD122 + T cells are responsible for the majority of IFN-g production, whereas CD8 + CD122 2 cells produce only small amounts of IFN-g ( Fig. 3C) [30,31]. Moreover, we found that after activation, CD8 + CD122 + T cells produce a great amount of perforin and granzyme B (Fig.…”

Novel mechanism of C‐reactive protein for enhancing mouse liver innate immunity†

“…Next, mice were injected intraperitoneally with IL‐12 (0.5 μg/mouse); 16 hours later, LPS (50 μg/mouse) was injected intravenously (GSR) into mice21, 22 that had been pretreated with CRP or PBS 1 hour before LPS injection. We examined several doses of CRP pretreatment (50, 250, or 500 μg) in this GSR model.…”

“…In fact, microsphere‐phagocytosing Kupffer cells still showed significantly higher TNF and ROS production than nonphagocytosing Kupffer cells even under CRP‐pretreated conditions. On the other hand, TNF is well known as a critical molecule that induces septic shock, MODS, and GSR associated with disseminated intravascular coagulation 21, 22, 26. However, presumably because Kupffer cells have to phagocytose a large amount of bacteria in lethal E. coli infection, TNF and ROS may need to be high.…”

The Effect of Synthetic C-Reactive Protein on the In Vitro Immune Response of Human PBMCs Stimulated with Bacterial Reagents

“…IFN-γ production from NK/NKT cells during the IL-12 priming phase, and TNF production from macrophages/Kupffer cells after LPS stimulation are crucial for this phenomenon [14]. Shwartzman reaction-like phenomenon can be reproduced in human PBMCs in vitro when they are cultured with IL-12 for 24 h and subsequently cultured with LPS for additional 24 h, in which a much larger amount of TNF is produced from macrophages than that produced from macrophages stimulated with LPS alone ( in vitro Shwartzman reaction) [6], which is confirmed in this study and synthetic CRP decreased this phenomenon.…”