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.
Kwiatkowski
B
B
Department of Surgery, Columbia-Presbyterian Medical Center, New York 10032, USA.
Artrip
J H
JH
Michler
R E
RE
Itescu
S
S
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha