Abstract
Although bone marrow represents the main site for NK cell development and also distinct thymic-dependentNK cell pathway was identified, the cytokines effect on the NK cell generation from cord blood is unclear. Studies were identified the role of cytokines in the regulation of bone marrow and thymic NK cells. Previous studies reported that IL15 are critical for bone marrow dependent and IL7 is important for thymic NK cells. It is remain unclear the cytokines influence on the expantion of NK cells in cord blood mononuclear cells. We evaluated cultured cord blood mononuclear cells suplememnted with combinations of cytokines using FACS in distinct time points. In this study, we presented the role of IL2, IL7 and IL15 as members of the common gamma receptor -chain (Il2rg) on the expansion NK cells from cord blood cells. By investigating cord blood mononuclear cells in vitro , we demonstrated that IL2 and IL15 are important for expansion of NK cells. IL2 in comparision with IL15 has more influences in NK cell expansion. In contrast IL-7 is dispensable for NK cell generation in cord blood. Thus,IL-2Rg cytokines play complementary roles and are indispensable for homeostasis of NK cell development in cord blood. Probably these cytokines could help to use NK beneficials in engrafment of transplanted cells and Anti tumor activity of NK cells.
Highlights
Natural Killer (NK) cells are large granular lymphocytes as a major compartmment of innate immunity, represent as a third lymphoid lineage.[1,2] They destroy stressed cells, tumor cells and virus infected cells without any immunization and pre activation.[3]
The 105 cord blood mononuclear cells were seeded in 96well plates in 200 μL of RPMI1640 (Gibco) including 20% fetal bovine serum (FBS; Gibco), 1% penicillin/streptomycin (Gibco), in addition supplemented with cytokines including SCF, Flt[3] ligand, IL- 7, IL-15, and IL-2
Mononuclear cells of umbilical cord blood can be efficiently expanded into NK Cells The IL2Rg cytokines(common cytokine receptor γ chain) including Il2, IL7 and IL15 have been shown previously to be important for NK cells development in bone marrow
Summary
Natural Killer (NK) cells are large granular lymphocytes as a major compartmment of innate immunity, represent as a third lymphoid lineage.[1,2] They destroy stressed cells, tumor cells and virus infected cells without any immunization and pre activation.[3]. The activating receptor NKp46 is expressed on all human NK cells and rarely on T cells.[5,6]. It is one of the best markers for NK cells characterization.[7] NK cell transferring is a best strategy for cancer immunotherapy which Killer immunoglobulin like receptors (KIRs) as inhibitory receptors for HLA class I play an essential role in the anti-leukemic effects of allogeneic NK cell transfer.[8] In addition, alloreactive NK cells eliminate residual host dendritic cells, prevent graft-versus-host-disease.[8] Because NK cells are a fraction of peripheral blood mononuclear cells, the development of methods to produce large numbers of functional NK cells could be useful to optimize NK-based therapies
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