Inhibition of TF activity protects embryos from aPL-induced inflammation and embryonic death. (A) Pregnant female mice treated on days 8 and 12 with aPL-IgG received either an anti-TF mAb (1H1) or a rat IgG2a. On day 15 of pregnancy, mice were killed, uteri were dissected, and fetal resorption rates calculated (number of resorptions/number of fetuses + number of resorptions). There were 6 to 8 mice in each group. Mice that received aPL-IgG had a high frequency of fetal resorption compared with those that received normal human IgG (P < .001). Treatment with anti-TF mAb 1H1 led to a significant reduction in the frequency of fetal resorption compared with those mice receiving aPL-IgG (P < .01). Error bars here and in panel F are SD. (B,C) Immunohistochemical analysis of C3 in sections of deciduas from mice treated with either aPL-IgG + IgG2a or aPL-IgG + anti-TF antibody. (B) In deciduas from aPL-IgG + IgG2a–treated mice, C3 deposits (brown) were present throughout decidual tissue surrounding the necrotic residual embryonic debris (ED). (C) In contrast, in mice treated with aPL-IgG plus anti-TF antibody, C3 deposition was less intense and limited to the ectoplacental cone (ec) and the embryos remained intact (E). (D,E) Immunohistochemical analysis for neutrophils in sections of deciduas from aPL-IgG and aPL-IgG + anti-TF mAb 1H1. (D) Intense staining for neutrophils (brown) was observed in deciduas from mice treated with aPL-IgG plus IgG2a. In contrast, less neutrophil infiltration was observed in deciduas from mice that had received aPL-IgG + anti-TF mAb 1H1 (E). Counterstain: hematoxylin. Original magnification × 500. (F) Pregnant mice expressing low levels of TF (mTF^−/−,hTF⁺) were treated on days 8 and 12 with aPL-IgG or NH-IgG. On day 15, fetal resorption rates were calculated. Approximately 40% of the embryos in control mice (mTF^+/−,hTF⁺) treated with aPL-IgG were resorbed. Mice expressing low activity of TF showed a reduction in aPL-induced fetal resorption frequency compared with control mice (*P < .001).