Human NK cells demonstrate increased adherence and lysis of porcine endothelium following activation with IL-2.

BACKGROUND: For clinical xenotransplantation of pig organs to be successful, the significant barriers of host cellular immunity against the pig will need to be overcome. Natural killer (NK) cells appear to play an important role in rejection of discordant xenografts, and IL-2 activated human NK cells are cytotoxic to human endothelium. We addressed the role of IL-2 activated human and baboon NK cells in the primate immune response to pig xenoantigens in vivo and in vitro. METHODS: Human natural killer (NK) cells were isolated from pooled human peripheral mononuclear cells (PBMC) using density gradient centrifugation method. Phenotype of isolated cells was confirmed by flow cytometry. Purified NK cells were than tasted for spontaneous and IL-2 augmented adhesion and lysis of cultured pig aortic endothelial cells (PAEC) monolayers in a short-term 51 Cr-release assay. The effects of human macrophage derived cytokines TNF alpha and IL-1 on adhesion of IL-2 activated NK cells were studied. RESULTS: Human NK cells demonstrate prominent adherent and lytic activity against pig endothelium, which can be significantly augmented by IL-2. Macrophage derived cytokines can further augment the adherent properties of these NK cells. CONCLUSIONS: These result suggest that human NK cells are likely to play a significant role in rejection of pig-to-human xenografts.