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Figure 1.

In vivo antibody mediated neutralization of IFN-γ protects from lethal SEB-induced TSS.

Age-matched HLA-DR3 transgenic mice were challenged with SEB (50 µg) immediately followed by indicated amounts of monoclonal rat anti-mouse IFN-γ or isotype control. Mice were closely monitored for symptoms of TSS.

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Figure 1 Expand

Figure 2.

Effect of antibody mediated neutralization of IFN-γ on SEB-induced cytokine and chemokine responses in vivo.

Age-matched HLA-DR3 transgenic mice were challenged with SEB (5 µg) immediately followed by 100 µg of goat anti-mouse IFN-γ or control goat antibodies. Mice were bled 3 hrs later and serum cytokine levels were determined using a multiplex suspension array system (Bio-Plex, Bio-Rad). Each bar represents the mean±SE of 4–6 mice.

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Figure 2 Expand

Figure 3.

Effect of antibody mediated neutralization of IFN-γ on SEB-induced splenic T cell expansion and thymocyte deletion.

Age-matched HLA-DR3 transgenic mice were challenged with SEB (5 µg) immediately followed by 100 µg of goat anti-mouse IFN-γ or control goat antibodies. Mice were killed 3 days later and distribution of different T cell subsets in the spleen (A and B) and thymus (C and D) was determined by flow cytometry. Each bar represents the mean±SE of 4–6 mice.

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Figure 3 Expand

Figure 4.

Effect of IFN-γ deficiency on SEB-induced TSS.

Age-matched HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice were challenged with SEB (50 µg) and monitored closely. Data from 6–13 mice in each group.

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Figure 4 Expand

Figure 5.

Effect of IFN-γ deficiency on SEB-induced cytokine responses in vivo.

Age-matched HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice were challenged with SEB (10 µg). Mice were bled at 3 hrs and serum cytokine levels were determined using a multiplex suspension array system (Bio-Plex, Bio-Rad).

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Figure 5 Expand

Figure 6.

Effect of IFN-γ deficiency on SEB-induced chemokine responses in vivo.

Age-matched HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice were challenged with SEB (10 µg). Mice were bled at 3 hrs and serum chemokine levels were determined using a multiplex suspension array system (Bio-Plex, Bio-Rad).

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Figure 6 Expand

Figure 7.

Effect of IFN-γ deficiency on SEB-induced splenic T cell expansion and thymocyte deletion.

Age-matched HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice were challenged with SEB (10 µg). Mice were killed 3 days later and distribution of different T cell subsets in the spleen (A and B) and thymus (C and D) was determined by flow cytometry. Each bar represents the mean±SE of 4–6 mice.

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Figure 7 Expand

Figure 8.

Effect of IFN-γ deficiency on SEB-induced pulmonary immunopathology.

Age-matched HLA-DR3.IFN-γ+/+ (A and C) and HLA-DR3.IFN-γ−/− (B and D) transgenic mice were left untreated (A and B) or challenged with SEB (50 µg, C and D). Mice were killed 48 hrs later, lungs were collected in buffered formalin and processed for H&E. The bar corresponds to 100 µM.

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Figure 8 Expand

Figure 9.

Effect of IFN-γ deficiency on SEB-induced hepatic immunopathology.

Age-matched HLA-DR3.IFN-γ+/+ (A to D) and HLA-DR3.IFN-γ−/− (E and H) transgenic mice were challenged with PBS (A, B and E, F) or challenged with SEB (50 µg) (C, D and G, H). Mice were killed 48 hrs later, livers were collected in buffered formalin and processed for H&E. The bar corresponds to 100 µM.

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Figure 9 Expand

Figure 10.

Effect of IFN-γ deficiency on SEB-induced intestinal immunopathology.

Age-matched HLA-DR3.IFN-γ+/+ (D, E and F) and HLA-DR3.IFN-γ−/− (G, H and I) transgenic mice were challenged with SEB (50 µg). Mice were killed 48 hrs later, intestinal segments were collected in buffered formalin and processed for H&E. Panels A, B and C – sections from naïve HLA-DR3.IFN-γ+/+ mice shown for comparison. The bar corresponds to 100 µM.

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Figure 10 Expand

Figure 11.

Effect of IFN-γ deficiency on SEB-induced duodenal immunopathology.

Age-matched HLA-DR3.IFN-γ+/+ (A, C and E) and HLA-DR3.IFN-γ−/− (B, D and F) transgenic mice were challenged with SEB (50 µg). Mice were killed at 24, 48 and 72 hrs, duodenal segments were collected in buffered formalin and processed for H&E. The bar corresponds to 100 µM.

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Figure 11 Expand

Figure 12.

Effect of IFN-γ deficiency on SEB-induced alteration in gut permeability.

Age-matched HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice were challenged with SEB (50 µg). Mice were gavaged with FITC-dextran as indicated in methods. Three hours after gavage, mice were killed, sera collected and the fluorescence in the sera were determined at 490 nm excitation and 525 nm emission.

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Figure 12 Expand