BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious adverse events following transfusion, and there is no specific treatment in clinical practice. However, regulatory T cells (Tregs) have been suggested to play a potential role in the treatment of TRALI. This study investigated whether interleukin (IL)-2 or IL-2/anti-IL-2 complexes (IL-2c), which are mediators of Treg expansion, can modulate the severity of antibody-mediated TRALI in vivo.
STUDY DESIGN AND METHODS:This study utilized a mouse model of the "two-hit" mechanism: BALB/c mice were primed with lipopolysaccharide (LPS) as the first hit, and then TRALI was induced by injecting major histocompatibility complex Class I antibodies. Mice injected with LPS only or LPS combined with isotype control antibodies served as controls. For the Tregdepleted groups, mice were infused with anti-mouse IL-2Rα first and then subjected to the same treatments as the TRALI group. Regarding IL-2-and IL-2c-treated mice, recombinant murine IL-2 or IL-2c was intraperitoneally administered to mice for 5 consecutive days before induction of the TRALI model. Samples were collected 2 hours after TRALI induction.
RESULTS: Prophylactic administration of IL-2 or IL-2cto mice prevented the onset of edema, pulmonary protein levels, and proinflammatory factors that inhibited polymorphonuclear neutrophil aggregation in the lungs. Furthermore, the percentage of CD4 + CD25 + FoxP3 + Tregs was expanded in vivo using IL-2 and IL-2c compared to TRALI mice, as was confirmed through analysis of the spleen, blood, and lung.
CONCLUSION:This study validates that the protective mechanisms against TRALI involve CD4 + CD25 + FoxP3 + Tregs, which can be expanded in vivo by IL-2 and IL-2c. This results in increased IL-10 levels and decreased IL-17A, thereby prophylactically preventing antibodymediated murine TRALI. ABBREVIATIONS: BALF = bronchoalveolar lavage fluid; HNA = human neutrophil antigen; IL = interleukin; IL-2c = IL-2/anti-IL-2 complexes; LPS = lipopolysaccharide; MPO = myeloperoxidase; MHC = major histocompatibility complex; Th17 = T helper 17; TRALI = transfusion-related acute lung injury; Tregs = regulatory T cells; W/D = wet-to-dry. From the