Figure 6.
Tregs and DCs suppress TRALI by stimulating secretion of IL-10, a novel therapeutic agent. (A) Plasma IL-10 levels in naive BALB/c mice or mice first treated (+) or not (−) with the indicated antibodies for Treg depletion and then injected with the TRALI-inducing antibody 34-1-2s or indicated control antibodies. (B) Plasma IL-10 levels of naive C57BL/6 mice or CD11c-DTR mice injected (+) or not (−) with the indicated reagents or antibodies. (C) CD4+CD25+FoxP3+ Treg levels in spleen and thymus and CD11c+ DCs in spleen of the same C57BL/6 mouse injected with isotype mouse IgG2a or 34-1-2s + AF6-88.5.5.3 (TRALI resistant). (D) Plasma IL-10 levels in WT C57BL/6 mice or IL-10 KO mice treated 34-1-2s + AF6-88.5.5.3. (E-I) Lung W/D weight ratios (E), body temperature (F), MIP-2 levels (G), pulmonary PMN percentages (H), and lung MPO enzyme activity (I) of WT C57BL/6 mice treated with 34-1-2s + AF6-88.5.5.3 or IL-10 KO mice treated with either isotype mouse immunoglobulin G2a (IgG2a) or 34-1-2s + AF6-88.5.5.3. (I) Lung W/D weight ratios of CD4+ T-cell–depleted C57BL/6 mice (J), Treg-depleted BALB/c mice (K), and DC-depleted CD11c-DTR mice (L) infused with 34-1-2s + AF6-88.5.5.3 and treated prophylactically with (+) or not (−) with murine IL-10 administration (45 µg/kg IV). (M) Lung W/D weight ratios of CD4+ T cell depleted C57BL/6 mice, infused with 34-1-2s + AF6-88.5.5.3, and treated therapeutically 15 minutes later with (+) or without (−) murine IL-10 administration (45 µg/kg IV) after onset of TRALI (at least 2-degree drop in rectal temperature 10 minutes after TRALI-antibody injection). All mice were analyzed 90 minutes the second injection. For the statistical analysis, only significant comparisons of interest are shown. The comparisons shown in panels A-B,E-I were analyzed a with 1-way ANOVA with Tukey’s post hoc test; panels D,J,L-M were analyzed with 1-tailed unpaired t test; and panel K was analyzed with a 1-tailed Mann-Whitney test. Each dot represents 1 mouse, and error bars represent SD. *P < .05, **P < .01, ***P < .001, ****P < .0001.

Tregs and DCs suppress TRALI by stimulating secretion of IL-10, a novel therapeutic agent. (A) Plasma IL-10 levels in naive BALB/c mice or mice first treated (+) or not (−) with the indicated antibodies for Treg depletion and then injected with the TRALI-inducing antibody 34-1-2s or indicated control antibodies. (B) Plasma IL-10 levels of naive C57BL/6 mice or CD11c-DTR mice injected (+) or not (−) with the indicated reagents or antibodies. (C) CD4+CD25+FoxP3+ Treg levels in spleen and thymus and CD11c+ DCs in spleen of the same C57BL/6 mouse injected with isotype mouse IgG2a or 34-1-2s + AF6-88.5.5.3 (TRALI resistant). (D) Plasma IL-10 levels in WT C57BL/6 mice or IL-10 KO mice treated 34-1-2s + AF6-88.5.5.3. (E-I) Lung W/D weight ratios (E), body temperature (F), MIP-2 levels (G), pulmonary PMN percentages (H), and lung MPO enzyme activity (I) of WT C57BL/6 mice treated with 34-1-2s + AF6-88.5.5.3 or IL-10 KO mice treated with either isotype mouse immunoglobulin G2a (IgG2a) or 34-1-2s + AF6-88.5.5.3. (I) Lung W/D weight ratios of CD4+ T-cell–depleted C57BL/6 mice (J), Treg-depleted BALB/c mice (K), and DC-depleted CD11c-DTR mice (L) infused with 34-1-2s + AF6-88.5.5.3 and treated prophylactically with (+) or not (−) with murine IL-10 administration (45 µg/kg IV). (M) Lung W/D weight ratios of CD4+ T cell depleted C57BL/6 mice, infused with 34-1-2s + AF6-88.5.5.3, and treated therapeutically 15 minutes later with (+) or without (−) murine IL-10 administration (45 µg/kg IV) after onset of TRALI (at least 2-degree drop in rectal temperature 10 minutes after TRALI-antibody injection). All mice were analyzed 90 minutes the second injection. For the statistical analysis, only significant comparisons of interest are shown. The comparisons shown in panels A-B,E-I were analyzed a with 1-way ANOVA with Tukey’s post hoc test; panels D,J,L-M were analyzed with 1-tailed unpaired t test; and panel K was analyzed with a 1-tailed Mann-Whitney test. Each dot represents 1 mouse, and error bars represent SD. *P < .05, **P < .01, ***P < .001, ****P < .0001.

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