A2AR 限制 IL-15 诱导的高细胞毒性 CD39(+) NK 细胞的生成

CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39 + NK cells in humans are not known.

We investigated the characteristics of human circulating CD39 + NK cells. In healthy donors, the proportion of circulating CD39 + NK cells in total NK cells was relatively low compared with that of CD39 - NK cells. Nonetheless, a higher proportion of CD39 + NK cells expressed CD107a.

Similarly, a higher proportion of CD39 + NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39 + NK cells to express higher levels of CD107a, IFN-γ and TNF-α, relative to CD39 - NK cells.

Importantly, IL-15 induced the generation of CD39 + NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39 + NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39 + NK cells, which have a stronger cytotoxicity than CD39 - NK cells. IL-15-induced human CD39 + NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells.