Inhibition of human NK-induced cell lysis and soluble cell-lytic molecules with anti-human LT antisera and various saccharides

The present study examines and compares the cytolysis of K-562 and MOLT-4 cells mediated by human natural killer (NK) cells from fresh peripheral blood and lymphotoxins (LT) derived from human lymphoid cell populations after lectin stimulation in vitro. Lymphotoxins were obtained from 5-hr concanavalin A (Con A)-restimulated human peripheral blood lymphocytes (PBL) which were precultured for 5 days in medium and fetal calf serum or with allogeneic human B-lymphoid cell lines. Two classes of probes were employed in both direct (cell) and indirect (supernatant) induced target-cell lysis: (a) various saccharides and (b) antibodies reactive with human LT forms. Two sugars, N-acetylglucosamine and alpha-methylmannoside, were able to inhibit direct cell lysis of both MOLT-4 and K-562 target cells. However, saccharide inhibition was distinct for each type of target even when effector cells were obtained from the same donor. These same saccharides were also able to inhibit 20-30% of the total LT activity in a supernatant for L-929 cells and 50-90% of the lytic activity on MOLT-4 cells. Anti-human F(ab')2 (IgG) and rabbit anti-alpha 2 LT sera blocked direct cell lysis of MOLT-4 and K-562 targets in 50% of the experiments. The anti-alpha 2 LT serum only recognizes a portion of the LT forms in these supernatants. These results reveal that, while both direct and indirect cell lysis are complex phenomena, they may both occur in some cases by a common mechanism(s)

Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Supernatants obtained from lectin-restimulated, preactivated, human peripheral blood lymphocytes rapidly released (5-24 hr) high levels of lymphotoxin (LT) activity in vitro. Peripheral blood lymphocytes were preactivated by coculturing with either fetal calf serum or with allogeneic continuous B-cell lines (LCCL) which were treated with mitomycin C. These supernatants contained a population of L-929 cell-lytic LT forms which also selectively bind to the NK-sensitive K-562 cell. However, lytic LT forms for L-929 cells from cPBL and LCCL cultures did not bind to the NK-sensitive MOLT-4 or NK-resistant Raji cells. Additional studies reveal these supernatants contain a second set of LT forms which have cell-binding and cell-lytic activity detectable on MOLT-4 and K-562 cells in a 12 to 18 hr 51Cr-release assay. Cell-lytic form(s) for the MOLT-4 and K-562 cells were not stable for more than a week at -20 degrees C. These findings indicate that materials with LT activity are heterogeneous with respect to their capacity to recognize common and discrete cell-surface components on different types of target cells in vitro

Studies on in vitro models of cellular immunity: The role of T and B cells in the secretion of lymphotoxin

When normal murine spleen cells were treated with anti-theta serum and complement, they failed to produce LT or synthesize cellular DNA when stimulated in vitro with PHA. Theta-positive cells were responsible for LT production in spleens removed from X-irradiated and bone marrow- or thymus-reconstituted animals. Finally, spleens from congenitally athymic Nu/Nu mice failed to produce LT when stimulated with pokeweed mitogen or phytohemagglutinin. © 1973

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Earthquake response and structural health monitoring of Christchurch Women's Hospital following the Canterbury and Christchurch earthquakes

The September 2010 Canterbury and February 2011 Christchurch earthquakes and associated aftershocks have shown that the isolator displacement in Christchurch Women's Hospital (Christchurch City's only base-isolated structure) was significantly less than expected. Occupant accounts of the events have also indicated that the accelerations within the hospital superstructure were larger than would usually be expected within a base-isolated structure and that residual low-level shaking lasts for a longer period of time following the strong-motion of an event than for non-isolated structures

The in vitro induction and release of a cell toxin by immune C57B1-6 mouse peritoneal macrophages.

Peritoneal macrophages from Sarcoma 1 (SAl)-sensitized CS7B1/6 mice release a toxic factor (s), termed macrophage toxic factor (MTF), into the medium when exposed to allogeneic target L cells in vitro. Medium containing MTF is cytotoxic to cultures of allogeneic L cells, syngeneic C57B1/6 fetal fibroblasts and xenogenic HeLa cells. The cell toxin (s) is insensitive to the effects of nuclease, neuraminidase and trypsin, but is partially abrogated by treatment with pronase. Two fractions of toxic activity are eluted from Sephadex G-100, one associated with a 150,000 mol wt marker (IgG), and the other associated with a 47,000 mol wt marker (ovalbumin). Goat antiserum prepared against PHA-induced mouse lymphotoxin (MLT) is capable of neutralizing the toxicity of both MTF and MLT, indicating that the factors may be similar. © 1972

Relationship of lymphotoxin secretion and DNA synthesis in the human mixed lymphocyte reaction in vitro

One-way mixed lymphocyte cultures employing human adenoid or peripheral blood lymphocytes activate lymphotoxin (LT)-secreting cells. Kinetic analysis of lymphocytes stimulated in mixed culture demonstrates that LT is secreted before the onset of DNA synthesis, but that maximum levels of LT secretion are reached simultaneously with maximum levels of DNA synthesis. Although the response of peripheral leukocytes is qualitatively similar to the response of adenoid-derived lymphocytes, unexplained high nonspecific background levels of toxic material(s) obscure early events in the former response. While cytochalasin B reversibly inhibits LT secretion, mitomycin C treated cultures are still capable of LT secretion. The results suggest that a population of cells exists, which does not require DNA synthesis to develop into effector cells. The requirement for DNA synthesis for the maximal development of effector cells may reside in a separate helper cell population as postulated by the two cell model of the mixed lymphocyte reaction. © 1975 Academic Press, Inc. All rights reserved