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. 2013 Oct 21;210(11):2223–2237. doi: 10.1084/jem.20131219

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© 2013 Bouchlaka et al.

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Figure 6. — TNF-dependent systemic toxicity after low-dose anti-CD40/IL-2 treatment. (A) Survival of aged (16 mo) C57BL/6 (WT), IFNR-KO, and TNF-KO mice that received low-dose anti-CD40/IL-2 or aged matched controls, n = 3–5. Survival analysis was plotted according to the Kaplan-Meier method, and statistical differences were determined with the log-rank test. (B–E) Serum cytokines and ALT levels from the aged WT and age-matched TNF-KO (12 mo) including TNF, IL-6, and IFN-γ and ALT after 2 d of treatment, n = 3. (F–H) Young C57BL/6 WT and TNF-KO (2 mo) mice (n = 3) were treated for 2 d with high-dose anti-CD40/IL-2 or control treatment, and liver histopathology (F and G) and serum ALT (H) levels were assessed for each group. (F) Representative H&E liver images with black arrows pointing to areas of necrosis. Bars: (top) 500 µm; (bottom) 200 µm. Statistical analysis was by one-way ANOVA. ***, P < 0.001; **, P < 0.01; *, P < 0.05. Bar graphs represent the mean ± SEM. (A–H) are representative of two independent experiments.