Characteristics of peripheral blood derived human cytokine-induced memory-like NK cells

NK cell;Cytokines;NK cell memory;CD62L(L-selectin);616.994

의과대학 협동과정 종양생물학전공 ;

University:서울대학교 대학원

关键词: NK cell;    Cytokines;    NK cell memory;    CD62L(L-selectin);    616.994;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/142376/1/000000151222.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Background: Recent studies have shown that natural killer (NK) cells have immunological memory after viral infection or in vitro cytokine stimulation. Cytokine-induced memory-like NK cells can be generated by short-term activation with IL-12, and IL-18. These NK cells secret more IFN-γ in response to re-stimulation of the cytokines. However, its mechanism has not fully understood yet. In this study, we investigated characteristics of cytokine-induced memory-like human NK cells.Methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were pre-activated with IL-12, and IL-18 or cultured with low dose of IL-15 (1 ng/ml) alone as a survival factor. The cells were washed and further cultured in fresh media containing low dose of IL-15 for 7 to 14 days. Phenotype and function of the NK cells were measured.Results: After 7 days, pre-activated NK cells secreted more IFN-g after cytokine re-stimulation. Compare to the control cells, a CD56bright CD62L+subset in NK cells was increased in these cells. As a CD56bright CD16- minor immature NK cell subset, but not major CD56dim CD16+ NK cells, also have same surface markers, we hypothesized that memory-like NK cells are derived from immature NK cells. By tracing with CFSE labeling, CD56bright CD62L+ NK cells were dramatically proliferated after cytokine stimulation compared to CD56dim CD16+ CD62L+/- NK cells. When purified CD56dim CD16+ CD62L- NK cells were culture after cytokine stimulation, these cells did not acquire CD62L expression. These data show that the CD62L+ memory-like NK cells derived from CD56bright CD62L+ immature NK cells but not major CD56dim NK cells. Although memory-like NK cells showed express more IFN-γ after co-culturing with K562 leukemia cells as well as cytokine re-stimulation, cytotoxicity measured by CD107a+ degranulation was similar to control NK cells.Conclusion: Our findings show that cytokine-induced memory-like NK cells are selectively expanded from a CD56bright immature NK cell subset by cytokines. As in vitro generated memory-like NK cell cell therapy are now under clinical trials, these finding may be useful for a use of NK cell-based therapy for cancer patients.