Donor-specific Blood Transfusion Induces a Transfusion-related Early Protective Effect in Murine Lung Transplantation

Abstract

Lung transplantation (LTx) remains limited by high immunogenicity and chronic rejection, yet the application of donor-specific blood transfusion (DSBT) in LTx has not been fully investigated. We established a murine orthotopic LTx model (BALB/c to C57BL/6N) to evaluate the safety and efficacy of DSBT administered 24 hours prior to transplantation. Pre-transplant transfusion was well-tolerated showing no evidence of Transfusion-Related Acute Lung Injury (TRALI) or volume-overload injury. Radiographic analysis at POD 7 demonstrated that DSBT-treated grafts maintained significantly higher aerated lung volume compared to non-transfused controls. Flow cytometric analysis at the same time point revealed that these grafts were preferentially infiltrated by recipient-derived monocytes and type 2 conventional dendritic cells (cDC2s), while lymphoid cell counts remained comparable across groups in both the lung and spleen, indicating no systemic immune depletion. By POD 35, however, histological analysis revealed that the lung grafts were extensively destroyed by severe rejection. These findings demonstrate that a 24-hour pre-transplant DSBT window improves early graft patency and modulating the localized myeloid landscape in a murine model. We conclude that DSBT serves as a safe and effective induction strategy to mitigate early inflammatory consolidation, providing a predictable temporal window for secondary immunomodulatory interventions in lung transplantation.