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

BACKGROUND: NK cells have been long time considered as cytotoxic lymphocytes competent in killing virus-infected cells and tumors. However, NK cells may also play essential immuno-regulatory functions. In this context, the real existence of a defined NK subset with negative regulatory properties has been hypothesized but never clearly demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we show the in vitro generation from human peripheral blood haematopoietic progenitors (PB-HP), of a novel subset of non-cytolytic NK cells displaying a mature phenotype and remarkable immuno-regulatory functions (NK-ireg). The main functional hallmark of these NK-ireg cells is represented by the surface expression/release of HLA-G, a major immunosuppressive molecule. In addition, NK-ireg cells secrete two powerful immuno-regulatory factors: IL-10 and IL-21. Through these factors, NK-ireg cells act as effectors of the down-regulation of the immune response: reconverting mature myeloid DC (mDC) into immature/tolerogenic DC, blocking cytolytic functions on conventional NK cells and inducing HLA-G membrane expression on PB-derived monocytes. The generation of "NK-ireg" cells is obtained, by default, in culture conditions favouring cell-to-cell contacts, and it is strictly dependent on reciprocal trans-presentation of membrane-bound IL-15 forms constitutively and selectively expressed by human CD34(+) PB-HP. Finally, a small subset of NKp46(+) HLA-G(+) IL-10(+) is detected within freshly isolated decidual NK cells, suggesting that these cells could represent an in vivo counterpart of the NK-ireg cells. CONCLUSIONS/SIGNIFICANCE: In conclusion, NK-ireg cells represent a novel truly differentiated non-cytolytic NK subset with a self-sustainable phenotype (CD56(+) CD16(+) NKp30(+) NKp44(+) NKp46(+) CD94(+) CD69(+) CCR7(+)) generated from specific pSTAT6(+) GATA3(+) precursors. NK-ireg cells could be employed to develop new immuno-suppressive strategies in autoimmune diseases, transplant rejection or graft versus host diseases. In addition, NK-ireg cells can be easily derived from peripheral blood of the patients and could constitute an autologous biotherapic tool to be used combined or in alternative to other immuno-regulatory cells

YBa₂Cu₃O_y Superconducting Ceramics Incorporated with Different Types of Oxide Materials as Promising Radiation Shielding Materials: Investigation of The Structure, Morphology, and Ionizing Radiations Shielding Performances

New series of YBCO ceramics samples doping with different oxides such as SiO2, WO3, Al2O3, and TiO2 were fabricated to study the ionizing radiation shielding properties. The structure and morphology were explored by X-ray diffraction (XRD) and scanning electron microscope (SEM). The shielding properties were investigated experimentally and theoretically to check the validity of the results. The investigated radiation shielding properties include the proton, neutron, and gamma-ray. The XRD results show the orthorhombic structure for all ceramics without any additional peaks related to WO3, SiO2, TiO2, and Al2O3. At the same time, the SEM results appear to have a significant differentiation in the granular behavior of all ceramics surfaces. The incorporation of WO3 to YBCO enhanced the ceramic density, whereas the addition of different oxides reduced the density for ceramic samples. This variation in density changed the radiation shielding results. The sample containing WO3 (YBCO-W) gives us better results in radiation shielding properties for gamma and neutron; the sample having Al2O3 (YBCO-Al) is superior in shielding results for charged particles. Finally, the possibility to use YBCO with various oxides in different ionizing radiation shielding fields can be concluded