IL-2: Fine-tuning the Germinal Center Reaction

T follicular cells help B cells to drive germinal center formation. In this issue of Immunity, Ballesteros-Tato et al. (2012) demonstrate that high amounts of interleukin-2 inhibit production of this critical T effector subset

ON THE MULTIPLE-SCALE ANALYSIS FOR SOME LINEAR PARTIAL q-DIFFERENCE AND DIFFERENTIAL EQUATIONS WITH HOLOMORPHIC COEFFICIENTS

International audienceThe analytic and formal solutions of certain family of q-difference-differential equations under the action of a complex perturbation parameter is considered. The previous study [10] provides information in the case when the main equation under study is factoriz-able, as a product of two equations in the so-called normal form. Each of them gives rise to a single level of q-Gevrey asymptotic expansion. In the present work, the main problem under study does not suffer any factorization, and a different approach is followed. More precisely, we lean on the technique developed in [4], where the first author makes distinction among the different q-Gevrey asymptotic levels by successive applications of two q-Borel-Laplace transforms of different orders both to the same initial problem and which can be described by means of a Newton polygon

Doping and band-gap engineering of an intrazeolite tungsten(VI) oxide supralattice

New results are presented concerning the topotactic self-assembly, n-type doping and band-gap engineering of an intrazeolite tungsten(VI) oxide supralattice n(W03)-Na56Y, where 0 < η < 32, built-up of single size and shape (W03)2 dimers. In particular it has been found that the oxygen content of these dimers can be quantitatively adjusted by means of a thermal vacuum induced reversible reductive-elimination oxidative-addition of dioxygen. This provides access to new n(W03.x)-Na56Y materials (0 < χ ^ 1.0) in which the oxygen content, structural properties and electronic architecture of the dimers are changed. In this way one can precisely control the oxidation state, degree of η-doping and band-filling of a tungsten(VI) oxide supralattice through an approach which can be considered akin to, but distinct in detail to, that found in the Magneli crystallographic shear phases of non-stoichiometric bulk W03.x . Another discovery concerns the ability to alter local electrostatic fields experienced by the tungsten(VI) oxide moieties housed in the 13Ä supercages of 16(W03)-M36Y, by varying the ionic potential of the constituent supercage M + cations across the alkali metal series. This method provides the first opportunity to fine-tune the band-gap of a tungsten(VI) oxide supralattice. Α miniband electronic description is advanced as a qualitative first attempt to understand the origin of the above effects. The implications of these discoveries are that cluster size, composition and intrinsic electrostatic field effects can be used to "chemically manipulate" (engineer) the doping and band architecture of intrazeolite supralattices of possible interest in quantum electronics and nonlinear optics

Regulation of nuclear factor-κ B and activator protein-1 activities after stimulation of T cells via glycosylphosphatidylinositol-anchored Ly-6A/E.

Cross-linking of glycosylphosphatidylinositol-anchored proteins, including mouse Ly-6A/E, leads to IL-2 secretion and T cell activation, whereas engagement of Ly-6A/E uniquely inhibits IL-2 production induced via TCR. However, little is known concerning the molecular mechanism by which glycosylphosphatidylinositol-anchored proteins regulate IL-2 expression. In this study, we have examined the ability of an anti-Ly-6A/E mAb to regulate transcription factors controlling IL-2 expression. Stimulation of EL4J(Ly-6E).A4 cells with anti-CD3 epsilon or anti-Ly6A/E mAbs induced nuclear factor (NF)-κ B p65-p50 (RelA/p50) and AP-1 (Fos/Jun) binding activities and increased nuclear factor of activated T cells (NF-AT) activity, whereas octamer-binding factor and NF-Y levels were stable. Cyclic AMP response element binding protein and T cell-specific factor-1 (α) activities were selectively enhanced by anti-CD3 epsilon, but not by anti-Ly6A/E, which suggests that signaling via the TCR and Ly-6 were not identical. Costimulation of these cells with both mAbs produced substantially reduced levels of AP-1, NF-AT, and, especially, NF-κ B p65-p50 whereas cyclic AMP response element binding protein and T cell-specific factor-1(α) were induced to a level seen after stimulation by anti-CD3 epsilon. The inducibility of the IL-2 enhancer in vivo and the contribution of individual transcription factors for this induction were assessed with use of reporter chloramphenicol acetyltransferase constructs containing the IL-2 enhancer or oligomerized binding sites for transcription factors. These experiments also demonstrated a key role for NF-κ B and AP-1 in the transcriptional regulation of the IL-2 gene by TCR- and Ly6A/E-mediated signaling. By using the 2B4.11 T cell hybridoma and a mutated variant, were revealed a crucial role for the zeta-chain in Ly6A/E-mediated activation of NF-κ B

Experimental Building Demonstration Model with Viscous Dampers

At the end of spring quarter, 2016, we were able to meet most of the objectives and complete basic testing of the structure, as described in the proposal. However, we were unable to complete a few things. Firstly, we were unable to fabricate supplemental beams and columns to be ready in the case a member needed to be replaced. Drawings will be provided so that future students or faculty can fabricate the members. Secondly, we were unable to run earthquake ground motions through the structure due to time constraints with the students graduating. Future graduate students in the ARCE department will be testing the structure next year by running various ground motions through the shake table and analyzing the performance to confirm the adequacy of the structure. Those experimental results will be compared with the calculations performed to see how accurate the analysis was. We were able to shake the model at its first mode of vibration during the spring quarter of 2016 and we were able to determine that the structure was constructed adequately. A complete report detailing the design and calculations has been uploaded to the digital commons

Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period

Although many aspects of CD4+CD25+ T regulatory (Treg) cell development remain largely unknown, signaling through the IL-2R represents one feature for the production of Treg cells. Therefore, the present study was undertaken to further define early developmental steps in the production of Treg cells, including a more precise view on the role of interleukin (IL)-2 in this process. After adoptive transfer of wild-type Treg cells into neonatal IL-2Rβ−/− mice, only a small fraction of donor Treg cells selectively seeded the lymph node (LN). These donor Treg cells underwent rapid and extensive IL-2–dependent proliferation, followed by subsequent trafficking to the spleen. Thus, IL-2 is essential for Treg cell proliferation in neonatal LN. The number and distribution of Treg cells in the periphery of normal neonatal mice closely paralleled that seen for IL-2Rβ−/− mice that received Treg cells. However, for normal neonates, blockade of IL-2 decreased Treg cells in both the thymus and LN. Therefore, two steps of Treg cell development depend upon IL-2 in neonatal mice, thymus production, and subsequent expansion in the LN

Pleiotropic effects of Bcl-2 on transcription factors in T cells: potential role of NF-_KB p50–p50 for the anti-apoptotic function of Bcl-2

Bcl-2 functions to repress apoptosis by regulation of genes which encode proteins required for programmed cell death and by interference with peroxidative damage. We investigated the interrelationship between expression of bcl-2 and regulation of transcription factor DNA binding activities in the 2B4 T cell hybridoma and IL-2-dependent CTLL T cell line. Over-expression of bcl-2 in 2B4 resulted in enhanced basal levels of activator protein (AP)-1, octamer binding factor (Oct)-1, lymphoid enhancer binding factor (LEF)-1, RelA-p50 and NF-_KB p50–p50 DNA binding activities. After apoptotic signaling, down-regulation of AP-1, NF-AT and Oct-1 binding activities was observed in control 2B4 and CTLL, whereas suboptimal, but higher, levels of these transcription factors were found in bcl-2-transfected cells, potentially promoting cell survival. Furthermore, after apoptotic signaling, expression of bcl-2 led to differential changes of NF-_KB levels, resulting in a decrease in RelA-p50 and an increase In NF-_KB p50–p50, altering the ratio of these DNA binding activities such that now p50–p50 markedly predominated in both 2B4-Bcl-2 and CTLL-Bcl-2. Apoptotic signaling in the presence or absence of Bcl-2 resulted in induction of the RelB-p50 heterodimer in 2B4. The changes in NF-_KB/ROI levels raise the possibility that this family of transcription factors may play an important role in the regulation of apoptosis

Regulation of Fas-Dependent Activation-Induced T cell Apoptosis by cAMP Signaling: A Potential Role for Transcription Factor NF-κB

TCR-mediated activation of T cell hybridomas induces programmed cell death by a Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the absence or presence of transgenic Bcl-2, with anti-CD3epsilon and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective down-regulation of the nuclear levels of NF-κB p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-κB activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-κB p65 antisense oligonucleotide down-regulated nuclear levels of NF-κB, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-κB in the regulation of activation-induced apoptosis in T lymphocytes

Experimental Building Demonstration Model With Viscous Fluid Dampers

The Architectural Engineering major places a heavy emphasis on structural dynamics and the role of wind and seismic loading in building analysis and design. Buildings of high importance that are critical to community function, such as hospitals, often utilize supplemental damping devices like supplemental viscous fluid dampers or base isolators to reduce the overall demands on the structural system. The design and analysis of these dampers are typically not taught at the undergraduate level, and is frequently performed by mechanical engineers, in lieu of structural engineers. To better understand and research building behavior with supplemental damping devices, our multi-disciplinary team designed and fabricated an interactive, reconfigurable, multi-story model of a building. This building structure was dynamically tested and analyzed using the ARCE Department’s seismic shake table. The building model will be left with the university to serve as a model for undergraduate students enrolled in ARCE 483 and ARCE 412. Students will work together to test the structure under a variety of conditions and compare the findings with predictions from computer models. This model also has the potential to be used in core mechanical engineering courses, such as the Mechanical Vibrations course, ME 318