Background: Natural killer (NK) cells are a critical component of the innate immune system and play a pivotal role in mediating immune responses to xenogeneic cells. This study aimed to assess the activity of a human NK cell line (NK92) against porcine endothelial cells and red blood cells (RBCs) to evaluate the feasibility of porcine RBC transfusion to humans.

Methods: Human NK92 cells were co-cultured with three types of endothelial cells: human endothelial cells, porcine endothelial cells (WT and TKO). Additionally, four types of RBCs were used: human RBCs and porcine RBCs (WT, GTKO and TKO). IFN-γ production was measured using a human IFN-γ ELISA kit (BD Biosciences, San Diego, CA, United States) in the supernatants at different time points: immediately after the addition of the cell suspension (day 0) and on days 1 and 3 of incubation. Comparisons were made between human and porcine cells to identify differences in NK cell activation.

Results: NK92 cells produced significantly higher IFN-γ in response to porcine endothelial cells, irrespective of WT or GTKO origin, compared to human endothelial cells (p < 0.05). In contrast, IFN-γ production by NK92 cells co-cultured with porcine RBCs was comparable to that observed with human RBCs, with no statistically significant difference. Furthermore, no differences in NK cell activation were observed between WT and GTKO porcine RBCs.

Summary/conclusions: Our findings demonstrate that while porcine endothelial cells activate human NK cells robustly, porcine RBCs do not provoke a comparable immune response. This differential activity underscores the potential of porcine RBCs as viable candidates for xenotransfusion. These data provide foundational insights into the immunological compatibility of porcine RBCs, supporting their further evaluation in preclinical models.