TL;DR: The monoclonal antibody HNK-1, produced against a membrane antigen from the cultured T cell line, HSB-2, defines the first differentiation antigen shown to be selectively expressed on human NK and K cells.
Abstract: A monoclonal IgM antibody (HNK-1) was produced against a membrane antigen from the cultured T cell line, HSB-2 By indirect immunofluorescence, this antibody reacted with certain human cultured T cell lines (HSB-2 and MOLT-4 but not MOLT-3) but not with other lines of B cell or phagocytic cell origin HNK-1 reacted with 151 +/- 71% of normal blood lymphocytes but was unreactive with monocytes, granulocytes, erythrocytes, and platelets HNK-1+ cells separated by a fluorescence-activated cell sorter (FACS) were a homogeneous population of medium sized lymphocytes with abundant neutrophilic cytoplasm containing azurophilic granules HNK-1+ cells were nonadherent, surface Ig-, mostly FcIgG receptor+ and both positive and negative for demonstrable sheep erythrocyte (E) rosetting capability Cell suspensions enriched for E-rosetting T cells and depleted of FcIgG receptor+ cells contained few (6%) HNK-1+ cells Depletion of HNK-1+ cells from blood mononuclear cell populations by complement (C) mediated lysis greatly reduced NK activity against K-562 target cells and K cell lytic activity against antibody-coated chicken red blood cells Treatment with HNK-1 alone or C alone did not affect these activities When the FACS was utilized to separate HNK-1+ and HNK-1- cells from 6 individuals, the HNK-1+ cell population contained almost all of the NK and K cell function The monoclonal antibody HNK-1 thus defines the first differentiation antigen shown to be selectively expressed on human NK and K cells
TL;DR: Findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.
Abstract: Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined. NKp46 is thought to be the main activating receptor for human NK cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.
TL;DR: It is demonstrated for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo, thereby promoting metastasis and surface shielding by platelet aggregates seems to be the main mechanism.
Abstract: Natural killer (NK) cells provide effective antitumoral activity in the blood stream of mice, leading to reduced metastasis. There are, however, tumor cells that metastasize despite the presence of an intact NK system. The capability of tumor cells to induce platelet aggregation, on the other hand, correlates with their enhanced metastatic potential. A counteractive role of platelets for the NK function in metastasis has never been conceived. Here we demonstrate for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo. Using three different tumor cell lines in a mouse model of experimental metastasis, tumor seeding in the target organs was reduced when the host was platelet depleted, but only if the tumor cells were NK sensitive. Aggregation of platelets around tumor cells also inhibited in vitro NK tumorilytic activity. This protection of tumor cells by platelets was mouse strain independent and was equally observed with platelets from β2-microglobulin-deficient mice, excluding a NK inhibitory function of MHC class I on platelets. Thus, even if tumor cells are NK susceptible and cytotoxic NK cells threaten their survival in the blood, platelets are capable of protecting them from cytolysis, thereby promoting metastasis. Surface shielding by platelet aggregates seems to be the main mechanism of this protection.
TL;DR: The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr 1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation.
Abstract: CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.
TL;DR: The functional importance of NK cell cytotoxicity and the receptor/ligand interactions that control these processes are discussed, which are important for the pathophysiology of many diseases.