Tα1-treated DCs protect from aspergillosis in experimental HSCT. Lethally irradiated C57BL/6 mice received at least 2 × 106 T-cell–depleted allogeneic bone marrow cells from BALB/c mice 2 weeks before the intratracheal injection of 2 × 108/80 μL saline Aspergillus conidia. One and 7 days after transplantation, mice received 5 × 105Aspergillus-pulsed GM- or FL-DCs grown in Tα1 (A) or purified DC populations from spleens (spDCs; B), intraperitoneally. *P < .05, mice receiving DCs versus untreated mice. Resistance to infection was assessed in terms of MST (median survival time in days) and fungal growth in the lung and brain (μg/organ glucosamine content, bars indicating standard errors) 3 days after infection or at the time of death. Also shown in figure are inflammatory lung pathology (C), occurrence of GVHD reactivity (D), and susceptibility to infection (E) in the presence of donor T cells. (C) Periodic acid–Schiff–stained sections were prepared from lungs of mice infected with Aspergillus conidia 3 days earlier either untreated (None) or receiving different types of DCs. Severe signs of bronchial wall damage and necrosis and scarce inflammatory cell recruitment were observed in the lungs of untreated or GM-DC–treated mice, as opposed to mice receiving Tα1-treated GM-DCs or FL-DCs, whose lungs were characterized by few healing infiltrates of inflammatory cells with no evidence of bronchial wall damage or inflammatory response. Original magnification, × 200 (obtained with a 20×/0.45 objective lens). (D) Pathology scores for representative mice receiving, with the graft, different numbers of donor T cells alone or together with different DC types. The degree of systemic GVHD was assessed by a scoring system that sums changes in 5 clinical parameters: weight loss, posture (hunching), activity, fur texture, and skin integrity (maximum index = 10). (E) Survival to infection in mice treated as in panel D.
