3,863 research outputs found
Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism
CD11b+ Gr-1+ myeloid suppressor cells (MSC) accumulate in lymphoid organs under conditions of intense immune stress where they inhibit T and B cell function. We recently described the generation of immortalized MSC lines that provide a homogeneous source of suppressor cells for dissecting the mechanism of suppression. In this study we show that the MSC lines potently block in vitro proliferation of T cells stimulated with either mitogen or antigenic peptide, with as few as 3% of MSC cells causing complete suppression. Inhibition of mitogenic and peptide-specific responses is not associated with a loss in IL-2 production or inability to up-modulate the early activation markers, CD69 and CD25, but results in direct impairment of the three IL-2R signaling pathways, as demonstrated by the lack of Janus kinase 3, STAT5, extracellular signal-regulated kinase, and Akt phosphorylation in response to IL-2. Suppression is mediated by and requires NO, which is secreted by MSC in response to signa..
Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes
We described a generalized suppression of CTL anamnestic responses that occurred in mice bearing large tumor nodules or immunized with powerful recombinant viral immunogens. Immune suppression entirely depended on GM-CSF-driven accumulation of CD11b(+)/Gr-1(+) myeloid suppressor cells (MSC) in secondary lymphoid organs. To further investigate the nature and properties of MSC, we immortalized CD11b(+)/Gr-1(+) cells isolated from the spleens of immunosuppressed mice, using a retrovirus encoding the v-myc and v-raf oncogenes. Immortalized cells expressed monocyte/macrophage markers (CD11b, F4/80, CD86, CD11c), but they differed from previously characterized macrophage lines in their capacities to inhibit T lymphocyte activation. Two MSC lines, MSC-1 and MSC-2, were selected based upon their abilities to inhibit Ag-specific proliferative and functional CTL responses. MSC-1 line was constitutively inhibitory, while suppressive functions of MSC-2 line were stimulated by exposure to the cytokine IL-4. Both MSC lines triggered the apoptotic cascade in Ag-activated T lymphocytes by a mechanism requiring cell-cell contact. Some well-known membrane molecules involved in the activation of apoptotic pathways (e.g., TNF-related apoptosis-inducing ligand, Fas ligand, TNF-alpha) were ruled out as candidate effectors for the suppression mechanism. The immortalized myeloid lines represent a novel, useful tool to shed light on the molecules involved in the differentiation of myeloid-related suppressors as well as in the inhibitory pathway they use to control T lymphocyte activation
Nitric oxide dependent inhibition of immune responses by immortalized myeloid suppressor cells
L-arginine metabolism in myeloid cells controls T-lymphocyte functions
Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways
Pozostalosci substancji aktywnych herbicydow Izoturon 500 SC i Segal 65 WG w glebie i roslinach pszenicy jarej
W pracy przedstawiono wyniki badań zawartości w glebie i roślinach pszenicy jarej substancji aktywnych: izoproturonu, metrybuzyny i amidosulfuronu, zawartych w herbicydach Izoturon 500 SC i Segal 65 WG. Doświadczenie przeprowadzono jako doświadczenie wazonowe z pszenicą jarą odmiany Koksa, stosując doglebowo Izoturon 500 SC (500 g izoproturonu w 1 dm³ preparatu) w dawkach: zalecanej przez producenta, pięciokrotnie i dwudziestopięciokrotnie większej. W fazie trzech liści pszenicy (21 dzień doświadczenia), dzień przed pierwszym pomiarem, wykonano dodatkowo oprysk Segalem 65 WG (50% metrybuzyny i 15% amidosulfuronu) w takich samych dawkach w jakich użyto Izoturon 500 SC. W fazie trzech liści, strzelania w źdźbło, kwitnienia i dojrzałości mlecznej pobierano próbki glebowe i roślinne, w których oznaczano w trzech powtórzeniach zawartość izoproturonu i amidosulfuronu metodą chromatografii cieczowej oraz zawartość metrybuzyny metodą chromatografii gazowej. Wyniki badań wskazują, że wśród badanych substancji aktywnych najdłuższym okresem zalegania w glebie charakteryzował się izoproturon. Natomiast zawartość w roślinach izoproturonu, metrybuzyny i amidosulfuronu była największa w fazie trzech liści i zmniejszała się w trakcie trwania doświadczenia. Ponadto po zastosowaniu herbicydów w dawce dwudziestopięciokrotnie większej od zalecanej po fazie trzech liści rośliny pszenicy uschły.Paper presents the results on studies on isoproturon, metribuzin and amidosulfuron contents in the soil and wheat plants, after the treatment with Izoturon 500 SC and Segal 65 WG herbicides.
In a pot experiment on spring wheat Koksa cv. the herbicide Izoturon 500 SC (500 g isoproturon per 1 dm³a preparation) was applied to the soil in three doses: recommended by the manufacturer, then 5 and 25 times larger. At the phase of three leaves (21st day of experiment) the plants were sprinkled with Segal 65 WG (50% metribuzin and 15% amidosulfuron) in the same doses as Izoturon 500 SC.
At the three leaf, shooting, ear formation and early maturity phases soil and plant samples were taken to determine the isoproturon and amidosulfuron contents using liquid chromatography and metribuzin content using gas chromatography. Obtained results showed that among studied active substances reminded in soil for isoproturon the longest time. However, the largest contents of isoproturon, metribuzin and amidosulfuron in plants were observed at three leaf phase and then they decreased during the experiment. Moreover, in the case of applying the herbicides at dose 25-times higher than recommended by the producer, the plants withered after the phase of three leaves
IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice
We previously demonstrated that a specialized subset of immature myeloid cells migrate to lymphoid organs as a result of tumor growth or immune stress, where they suppress B and T cell responses to Ags. Although NO was required for suppression of mitogen activation of T cells by myeloid suppressor cells (MSC), it was not required for suppression of allogenic responses. In this study, we describe a novel mechanism used by MSC to block T cell proliferation and CTL generation in response to alloantigen, which is mediated by the enzyme arginase 1 (Arg1). We show that Arg1 increases superoxide production in myeloid cells through a pathway that likely utilizes the reductase domain of inducible NO synthase (iNOS), and that superoxide is required for Arg1-dependent suppression of T cell function. Arg1 is induced by IL-4 in freshly isolated MSC or cloned MSC lines, and is therefore up-regulated by activated Th2, but not Th1, cells. In contrast, iNOS is induced by IFN-γ and Th1 cells. Because Arg1 and iNOS share L-arginine as a common substrate, our results indicate that L-arginine metabolism in myeloid cells is a potential target for selective intervention in reversing myeloid-induced dysfunction in tumor-bearing hosts
Investigation of the prevalence and role of mobile genetic elements associated with an aminoglycoside resistance gene, aacC2a, in Acinetobacter baumannii
Includes abstract.
Includes bibliographical references (leaves 115-141)
Entanglement and quantity in quantum space - About quantum measurement (II)
As a continuation and extension of "quantity in phase space" "quantity in quantum space" is introduced. With that, the disappearing of quantum interference discussed in a previous paper [S. Durr, et al., Nature 395 (1998) 33] is explained in the same spirit as our recent papers [Ren De-Ming, Commun. Theor. Phys. (Beijing, China) 41 (2004) 685, 833].Physics, MultidisciplinarySCI(E)中国科学引文数据库(CSCD)1ARTICLE133-364
Sneutrino DM in the NMSSM with inverse seesaw mechanism
In supersymmetric theories like the Next-to-Minimal Supersymmetric Standard Model (NMSSM), the lightest neutralino with bino or singlino as its dominant component is customarily taken as dark matter (DM) candidate. Since light Higgsinos favored by naturalness can strength the couplings of the DM and thus enhance the DM-nucleon scattering rate, the tension between naturalness and DM direct detection results becomes more and more acute with the improved experimental sensitivity. In this work, we extend the NMSSM by inverse seesaw mechanism to generate neutrino mass, and show that in certain parameter space the lightest sneutrino may act as a viable DM candidate, i.e. it can annihilate by multi-channels to get correct relic density and meanwhile satisfy all experimental constraints. The most striking feature of the extension is that the DM-nucleon scattering rate can be naturally below its current experimental bounds regardless of the higgsino mass, and hence it alleviates the tension between naturalness and DM experiments. Other interesting features include that the Higgs phenomenology becomes much richer than that of the original NMSSM due to the relaxed constraints from DM physics and also due to the presence of extra neutrinos, and that the signatures of sparticles at colliders are quite different from those with neutralino as DM candidate.National Natural Science Foundation of China (NNSFC) [11575053]SCI(E)ARTICLE1
Classical mechanics and quantum mechanics
The Newton equation of motion is derived from quantum mechanics.Physics, MultidisciplinarySCI(E)中国科学引文数据库(CSCD)2ARTICLE5685-6884
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