Generation of CD2<SUP>+</SUP>CD8<SUP>+</SUP> NK Cells from c-Kit<SUP>+</SUP> Bone Marrow Cells in Porcine
Generation of CD2<SUP>+</SUP>CD8<SUP>+</SUP> NK Cells from c-Kit<SUP>+</SUP> Bone Marrow Cells in Porcine
- Kyu Hee Lim Ji-Hui Han Yoon Seok Roh Bumseok Kim Jung-Kee Kwon Myoung Jo You Ho Jae Han Sohail Ejaz
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제16권 제3호
- 등재여부 : KCI등재
- 2012.01
- 167 - 174 (8 pages)
Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. Because bone marrow-derived hematopoietic stem cells (HSCs), lymphoid protenitors, can give rise to NK cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that porcine c-kit<sup>+</sup> bone marrow cells (c-kit<sup>+</sup> BM cells) develop into NK cells in vitro in the presence of various cytokines [interleukin (IL)-2, IL-7, IL-15, IL-21, stem cell factor (SCF), and fms-like tyrosine kinase-3 ligand (FLT3L)]. Adding hydrocortisone (HDC) and stromal cells greatly increases the frequency of c-kit<sup>+</sup> BM cells that give rise to CD2<sup>+</sup>CD8<sup>+</sup> NK cells. Also, intracellular levels of perforin, granzyme B, and NKG2D were determined by RT-PCR and western blotting analysis. It was found that of perforin, granzyme B, and NKG2D levels significantly were increased in cytokine-stimulated c-kit<sup>+</sup> BM cells than those of controls. And, we compared the ability of the cytotoxicity of CD2<sup>+</sup>CD8<sup>+</sup> NK cells differentiated by cytokines from c-kit<sup>+</sup> BM cells against K562 target cells for 28 days. Cytokines-induced NK cells as effector cells were incubated with K562 cells as target in a ratio of 100:1 for 4 h once a week. In results, CD2<sup>+</sup>CD8<sup>+</sup> NK cells induced by cytokines and stromal cells showed a significantly increased cytotoxicity 21 days later. Whereas, our results indicated that c-kit<sup>+</sup> BM cells not pretreated with cytokines have lower levels of cytotoxicity. Taken together, this study suggests that cytokines-induced NK cells from porcine c-kit<sup>+</sup> BM cells may be used as adoptive transfer therapy if the known obstacles to xenografting (e.g. immune and non-immune problems) were overcome in the future.