[Aim] The role of NK cells in pathophysiology of HCV infection was not entirely clear. Understanding the function of NK cells in HCV-infected patients may support clinical choices for optimal treatment. We investigated phenotypic and functional features of peripheral blood (PB) and intrahepatic (IH) NK cells from liver transplantation (LT) recipients and their corresponding donors.

[Methods] Twenty living donor LT recipients and their corresponding donors were enrolled in this study. Primary diseases were related to HCV, HBV, and others (13, 3, and 4 patients, respectively). According to the Child-Pugh criteria, 6 and 14 patients were classified as A/B group and C group, respectively. We performed ex vivo perfusion of the cirrhotic liver and the liver allograft through the portal vein. IH lymphocytes were extracted from these perfusates. We investigated the relevance of the phenotypic features of these IH and PB NK cells to the primary diseases, liver function, and variation in post- HCV RNA titer in HCV-infected patients.

[Results] Flow cytometry revealed that IH NK cells from LT recipients displayed unique phenotypic features, i.e. remarkably reduced expression of NKp46 and NKG2D, the activating receptors, in comparison to healthy donors. IH NK cells from the Child-Pugh C group showed further reduced expression of these receptors, in comparison to the Child-Pugh A/B group (p<0.05). Conversely, expression of CD158a, CD158b, and NKG2A, the inhibitory receptors, were maintained in IH NK cells even in the cirrhotic livers. There were no similar changes in PB NK cells. Unexpectedly, we found a bimodal distribution even among healthy donors in terms of NKp46 expression on IH NK cells. Of the 13 donors corresponding to the HCV-infected LT recipients, 7 had NKp46^high-expressing IH NK cells and the other 6 had NKp46^low-expressing IH NK cells. Of note, all of the 6 LT recipients of NKp46^high liver showed reduced serum HCV RNA titers at 1 week after LT, whereas 5 of the 7 LT recipients of NKp46^low liver showed elevated titers at this time point (P= 0.013). This remarkable difference was no longer observed beyond 2 weeks post-LT.[Conclusions] The expression of NKp46 on IH NK cells was negatively modulated in cirrhotic livers. NKp46^high NK cells in liver allografts were associated with a transient reduction of HCV viral load. These findings support our current proposal for preventing HCV reinfection by adoptive immunotherapy with donor-derived IH NK cells.

« Back to 2013 American Transplant Congress