Generation of a Novel Regulatory NK Cell Subset from Peripheral Blood CD34+ Progenitors Promoted by Membrane-Bound IL-15

摘要: Background: NK cells have been long time considered as cytotoxic lymphocytes competent in killing virus-infected and tumors. However, may also play essential immuno-regulatory functions. In this context, the real existence of a defined subset with negative regulatory properties has hypothesized but never clearly demonstrated. Methodology/Principal Findings: Herein, we show vitro generation from human peripheral blood haematopoietic progenitors (PB-HP), novel non-cytolytic displaying mature phenotype remarkable immunoregulatory functions (NK-ireg). The main functional hallmark these NK-ireg is represented by surface expression/ release HLA-G, major immunosuppressive molecule. addition, secrete two powerful factors: IL-10 IL-21. Through factors, act effectors down-regulation immune response: reconverting myeloid DC (mDC) into immature/tolerogenic DC, blocking cytolytic on conventional inducing HLA-G membrane expression PB-derived monocytes. ‘‘NK-ireg’’ obtained, default, culture conditions favouring cell-to-cell contacts, it strictly dependent reciprocal trans-presentation membrane-bound IL-15 forms constitutively selectively expressed CD34 + PB-HP. Finally, small NKp46 detected within freshly isolated decidual cells, suggesting that could represent an