Human Natural Killer Cells Account for Non-MHC Class I-Restricted Cytolysis of Porcine Cells

Despite similarities in the cellular response to allografts and xenografts, some aspects of the xenogeneic immune response are unique. We find that both freshly isolated and primed human peripheral blood lymphocytes manifest MHC unrestricted cytolysis of porcine cells. While natural antibody-mediated mechanisms account for variable levels of cytotoxicity, reproducible killing in the absence of human serum is attributable to natural killer (NK) cells. This was shown by cold target inhibition with K562 cells, increased anti-porcine cytotoxicity after enrichment for CD56+cells, and significantly reduced lytic activity after depletion of CD56+cells. Increased anti-porcine cytotoxicity after mixed culture of human and porcine cells was due to differentiation of NK cells to lymphokine-activated killer (LAK) cells and was IL-2 dependent. After depletion of NK cells, T-cell-mediated anti-porcine cytotoxicity could also be demonstrated. We conclude that the human anti-porcine cellular cytotoxic response is due to multiple cell types that include T cells in addition to NK and LAK cells.