53 research outputs found

    CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8+ T Cells to Generate Effector but Not Memory T cells

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    Background: The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8 + T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8 + T cell response have not been thoroughly evaluated. Methodology/Principal Findings: In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naïve CD8 + T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naïve CD8 + T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a Listeria monocytogenes infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8 + memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8 + memory T cells. Our results also suggest that inefficient generation of CD8 + memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8 + T cell response. Conclusions: Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cel

    IL-21 Limits Peripheral Lymphocyte Numbers through T Cell Homeostatic Mechanisms

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    IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents.To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non-autoimmune C57BL/6 and autoimmune NOD mice. Our data indicate that IL-21R knockout C57BL/6 and NOD mice show increased size of their lymphocyte population and decreased homeostatic proliferation. In addition, our experimental results demonstrate that IL-21 inhibits T cell survival. These data suggest that IL-21 acts to limit the size of the T cell pool. Furthermore, our data suggest IL-21 may contribute to the development of autoimmunity.Taken together, our results suggest that IL-21 plays a global role in regulating T cell homeostasis, promoting the continuous adaptation of the T cell lymphoid space

    Muon (g-2) Technical Design Report

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    The Muon (g-2) Experiment, E989 at Fermilab, will measure the muon anomalous magnetic moment a factor-of-four more precisely than was done in E821 at the Brookhaven National Laboratory AGS. The E821 result appears to be greater than the Standard-Model prediction by more than three standard deviations. When combined with expected improvement in the Standard-Model hadronic contributions, E989 should be able to determine definitively whether or not the E821 result is evidence for physics beyond the Standard Model. After a review of the physics motivation and the basic technique, which will use the muon storage ring built at BNL and now relocated to Fermilab, the design of the new experiment is presented. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2/3 approval

    Measurement of the Positive Muon Anomalous Magnetic Moment to 0.46 ppm

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    We present the first results of the Fermilab Muon g-2 Experiment for the positive muon magnetic anomaly aμ(gμ2)/2a_\mu \equiv (g_\mu-2)/2. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ωa\omega_a between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ω~p{\tilde{\omega}'^{}_p} in a spherical water sample at 34.7^{\circ}C. The ratio ωa/ω~p\omega_a / {\tilde{\omega}'^{}_p}, together with known fundamental constants, determines aμ(FNAL)=116592040(54)×1011a_\mu({\rm FNAL}) = 116\,592\,040(54)\times 10^{-11} (0.46\,ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both μ+\mu^+ and μ\mu^-, the new experimental average of aμ(Exp)=116592061(41)×1011a_\mu({\rm Exp}) = 116\,592\,061(41)\times 10^{-11} (0.35\,ppm) increases the tension between experiment and theory to 4.2 standard deviationsComment: 10 pages; 4 figure
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