Figure 7
Figure 7. Rescue of perforin−/−DC-Fas−/− mice from lethal inflammation by neutralization of IFN-γ. (A) Perforin−/−DC-Fas−/− mice (5 mice/group) were injected with anti–IFN-γ (200 μg/mouse) or rat IgG control intraperitoneally once every 2 days starting from 3 weeks of age. The survival of the mice was plotted. (B-E) Seven-week-old perforin−/−DC-Fas−/− mice or controls with or without anti–IFN-γ treatment as in panel A were used for blood analyses (B), measurement of cytokines by multiplex (C), flow cytometry analyses (D), and H&E staining for tissue sections (E). **P < .01. Statistic comparison between control and anti–IFN-γ treatment: for all cytokines except IL-12, P < .01; for IL-12, not significant. Scale bar in panel E: 50 μm. (F) A diagram for T cell–mediate killing of DCs in the prevention of inflammation. When perforin and Fas-dependent killing of DCs is inhibited, overactivation of T cells leads to IFN-γ production. IFN-γ then triggers a cascade of inflammation by activating macrophages and other cell types to produce different inflammatory cytokines and chemokines.

Rescue of perforin−/−DC-Fas−/− mice from lethal inflammation by neutralization of IFN-γ. (A) Perforin−/−DC-Fas−/− mice (5 mice/group) were injected with anti–IFN-γ (200 μg/mouse) or rat IgG control intraperitoneally once every 2 days starting from 3 weeks of age. The survival of the mice was plotted. (B-E) Seven-week-old perforin−/−DC-Fas−/− mice or controls with or without anti–IFN-γ treatment as in panel A were used for blood analyses (B), measurement of cytokines by multiplex (C), flow cytometry analyses (D), and H&E staining for tissue sections (E). **P < .01. Statistic comparison between control and anti–IFN-γ treatment: for all cytokines except IL-12, P < .01; for IL-12, not significant. Scale bar in panel E: 50 μm. (F) A diagram for T cell–mediate killing of DCs in the prevention of inflammation. When perforin and Fas-dependent killing of DCs is inhibited, overactivation of T cells leads to IFN-γ production. IFN-γ then triggers a cascade of inflammation by activating macrophages and other cell types to produce different inflammatory cytokines and chemokines.

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