NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease.

The CD94/NKG2 complex is expressed on T and NK lymphocytes. CD94 molecules covalently associate to activating or inhibitory NKG2 molecules, and their expression finely tunes cell responses. Human γδ T cells express several NKRs.

Mitochondrial function is related to alterations at brain SPECT in depressed patients.

Introduction: 99mTc-d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function.

PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway.

Although membrane phospholipid phosphatidylinositol-4,5bisphosphate (PIP2) plays a key role as signaling intermediate and coordinator of actin dynamics and vesicle trafficking, it remains completely unknown its involvement in the activation of cytolytic machinery. By live confocal imaging of primary human natural killer (NK) cells expressing the chimeric protein GFP-PH, we observed, during effector-target cell interaction, the consumption of a preexisting PIP2 pool, which is critically required for the activation of cytolytic machinery. We identified type I phosphatidylinositol-4-phosphate-5-kinase (PI5KI) alpha and gamma isoforms as the enzymes responsible for PIP2 synthesis in NK cells.

Increased frequency of human leukocyte antigen-E inhibitory receptor CD94/NKG2A-expressing peritoneal natural killer cells in patients with endometriosis.

Objective: To analyze the frequency of peritoneal natural killer (NK) cells expressing the human leukocyte antigen (HLA)-E receptor CD94/NKG2A in patients with endometriosis.

Design: Case-control study.

Setting: University hospital.

High-efficient lentiviral vector-mediated gene transfer into primary human NK cells.

Objective: The long-term transfection of genes into primary natural killer (NK) cells without disrupting normal cellular functions has been proven to be difficult with currently available gene-transfer methods. In this study, we establish a lentiviral vector-based technique for improved gene transfer into human NK cells in vitro and we report on high-efficient transduction of freshly isolated as well as cultured primary NK cells.

Methods: Freshly isolated or primary cultured human NK cells, as well as the human NK cell line YTS, were transduced with replication-incompetent human immunodeficiency virus (HIV)-based lentiviral vector bearing a GFP reporter gene or a gene of interest under the control of the elongation factor 1alpha (EF1alpha) promoter.

Arf6: a new player in FcgammaRIIIA lymphocyte-mediated cytotoxicity.

The activation of phosphoinositide metabolism represents a critical step in the signaling pathways leading to the activation of cytolytic machinery, but its regulation is partially understood. We report here that the stimulation of the low-affinity receptor for immunoglobulin G (IgG) (FcgammaRIIIA, CD16) on primary human natural killer (NK) cells induces a phosphatidylinositol 3-kinase (PI3K)-dependent activation of the small G protein Arf6. We first demonstrate a functional role for Arf6-dependent signals in the activation of the antibody-dependent cellular cytotoxicity (ADCC) attributable to the control of secretion of lytic granule content.