Impaired Plasmacytoid Dendritic Cell (PDC)-NK Cell Activity in Viremic Human Immunodeficiency Virus Infection Attributable to Impairments in both PDC and NK Cell Function▿

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections impair plasmacytoid dendritic cell (PDC) and natural killer (NK) cell subset numbers and functions, though little is known about PDC-NK cell interactions during these infections. We evaluated PDC-dependent NK cell killing and gamma interferon (IFN-γ) and granzyme B production, using peripheral blood mononuclear cell (PBMC)-based and purified cell assays of samples from HCV- and HIV-infected subjects. CpG-enhanced PBMC killing and IFN-γ and granzyme B activity (dependent on PDC and NK cells) were impaired in viremic HIV infection. In purified PDC-NK cell culture experiments, CpG-enhanced, PDC-dependent NK cell activity was cell contact and IFN-α dependent, and this activity was impaired in viremic HIV infection but not in HCV infection. In heterologous PDC-NK cell assays, impaired PDC-NK cell killing activity was largely attributable to an NK cell defect, while impaired PDC-NK cell IFN-γ-producing activity was attributable to both PDC and NK cell defects. Additionally, the response of NK cells to direct IFN-α stimulation was defective in viremic HIV infection, and this defect was not attributable to diminished IFN-α receptor expression, though IFN-α receptor and NKP30 expression was closely associated with killer activity in viremic HIV infection but not in healthy controls. These data indicate that during uncontrolled HIV infection, PDC-dependent NK cell function is impaired, which is in large part attributable to defective IFN-α-induced NK cell activity and not to altered IFN-α receptor, NKP30, NKP44, NKP46, or NKG2D expression

{2,6-Bis[(2,6-diisopropylphosphanyl)oxy]-4-fluorophenyl-κ3P,C1,P′}(1H-pyrazole-κN2)nickel(II) hexafluorophosphate

The title compound, [Ni(C18H30FO2P2)(C3H4N2)]PF6, was prepared by halide abstraction with TlPF6 in the presence of CH3CN in CDCl3 from the respective neutral pincer chlorido analogue followed by addition of pyrazole. The PO—C—OP pincer ligand acts in typical trans-P2 tridentate fashion to generate a distorted square-planar nickel structure. The Ni—N(pyrazole) distance is 1.925 (2) Å and the plane of the pyrazole ligand is rotated 56.2 (1)° relative to the approximate square plane surrounding the NiII center in which the pyrazole is bound to the NiII atom through its sp2-hybridized N atom. This Ni—N distance is similar to bond lengths in the other reported NiII pincer-ligand square-planar pyrazole complex structures; however, its dihedral angle is significantly larger than any of those for the latter set of pyrazole complexes