CD4+CD25+FoxP3+T-regulatory cells and CD11c+ dendritic cells protect against antibody-mediated murine TRALI.
Murine TRALI is associated with reduced IL-10 levels and IL-10 administration prevents and rescues TRALI development.
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by acute respiratory distress following blood transfusion. Donor antibodies are frequently involved, however, the pathogenesis and protective mechanisms in the recipient are poorly understood and specific therapies are lacking. Using newly developed murine TRALI models based on injection of anti-MHC class I antibodies, we found CD4+CD25+FoxP3+ T-regulatory cells (Tregs) and CD11c+ dendritic cells (DCs) to be critical effectors that protect against TRALI. Treg- or DC-depletion in vivo resulted in aggravated antibody-mediated acute lung injury within 90 minutes with 60% mortality upon DC-depletion. In addition, resistance to antibody-mediated TRALI was associated with increased IL-10 levels and IL-10 levels were found to be decreased in mice suffering from TRALI. Importantly, IL-10 injection completely prevented and rescued the development of TRALI in mice and may prove to be a promising new therapeutic approach for alleviating lung injury in this serious complication of transfusion.
- Submitted December 19, 2016.
- Accepted February 9, 2017.
- Copyright © 2017 American Society of Hematology
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