Differential Function of Natural Killer Cells in the Liver Graft Perfusate of Korean Population

Background

Liver perfusate (LP) lymphocytes show unique subsets compared with peripheral blood (PB) lymphocytes. LP natural killer (NK) and NKT cells may display unique cytotoxicity and cytokine production, thus leading to distinct roles in liver transplantation. In this study, we sought to evaluate the functions of graft perfusate NK and NKT cells in clinical liver transplantation.

Methods

The living donor right lobe graft was initially washed with 1 L of histidine-tryptophan-ketoglutarate solution to collect the perfusate. We also collected donor PB. Lymphocytes separated by the Ficoll-Hypaque density gradient method underwent immunophenotyping using multicolor flow cytometry. To assess cytokine secretion, we performed the enzyme-linked immunosorbent assay.

Results

There were more NK and NKT cells in LP confirming previous reports. In particular, CD56^brightCD16^low NK cells accounted for approximately 50% of total NK cells compared with 5% to 10% among PB NK cells. In response to cytokine stimulation LP NK cells produce tumor necrosis factor–α at different levels and less interleukin-10 compared with PB NK cells. The major source of interferon-γ production upon stimulation with liver caner cells were CD56^dim NK cells and CD56⁻CD3⁻ cells rather than NKT or T cells. Unlike PB NK cells, LP CD56^brightCD16^low NK cells along with CD56^dimCD16^high NK cells and NKT cells were efficient killers against Korean liver cancer cells.

Conclusion

LP NK and NKT cells showed unique functions in cytotoxicity and cytokine production.