1,140 research outputs found

    Diverse Roles of Inhibitor of Differentiation 2 in Adaptive Immunity

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    The helix-loop-helix (HLH) transcription factor inhibitor of DNA binding 2 (Id2) has been implicated as a regulator of hematopoiesis and embryonic development. While its role in early lymphopoiesis has been well characterized, new roles in adaptive immune responses have recently been uncovered opening exciting new directions for investigation. In the innate immune system, Id2 is required for the development of mature natural killer (NK) cells, lymphoid tissue-inducer (LTi) cells, and the recently identified interleukin (IL)-22 secreting nonconventional innate lymphocytes found in the gut. In addition, Id2 has been implicated in the development of specific dendritic cell (DC) subsets, decisions determining the formation of αβ and γδ T-cell development, NK T-cell behaviour, and in the maintenance of effector and memory CD8+ T cells in peripheral tissues. Here, we review the current understanding of the role of Id2 in lymphopoiesis and in the development of the adaptive immune response required for maintaining immune homeostasis and immune protection

    Transcriptional Regulation of Dendritic Cell Diversity

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    Dendritic cells (DCs) are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration, and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These findings open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now sets the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection

    Techniques for measuring atmospheric aerosols at the High Resolution Fly's Eye experiment

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    We describe several techniques developed by the High Resolution Fly's Eye experiment for measuring aerosol vertical optical depth, aerosol horizontal attenuation length, and aerosol phase function. The techniques are based on measurements of side-scattered light generated by a steerable ultraviolet laser and collected by an optical detector designed to measure fluorescence light from cosmic-ray air showers. We also present a technique to cross-check the aerosol optical depth measurement using air showers observed in stereo. These methods can be used by future air fluorescence experiments.Comment: Accepted for publication in Astroparticle Physics Journal 16 pages, 9 figure

    Evidence for virtual Compton scattering from the proton

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    In virtual Compton scattering an electron is scattered off a nucleon such that the nucleon emits a photon. We show that these events can be selected experimentally, and present the first evidence for virtual Compton scattering from the proton in data obtained at the Stanford Linear Accelerator Center. The angular and energy dependence of the data is well described by a calculation that includes the coherent sum of electron and proton radiation

    Momentum Transfer Dependence of Nuclear Transparency from the Quasielastic ^(12)C(e, e'p) Reaction

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    The cross section for quasielastic ^(12)C(e,e’p) scattering has been measured at momentum transfer Q^2=1, 3, 5, and 6.8 (GeV/c)^2. The results are consistent with scattering from a single nucleon as the dominant process. The nuclear transparency is obtained and compared with theoretical calculations that incorporate color transparency effects. No significant rise of the transparency with Q^2 is observed

    Report of the Working Group on the Composition of Ultra High Energy Cosmic Rays

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    For the first time a proper comparison of the average depth of shower maximum (XmaxX_{\rm max}) published by the Pierre Auger and Telescope Array Observatories is presented. The XmaxX_{\rm max} distributions measured by the Pierre Auger Observatory were fit using simulated events initiated by four primaries (proton, helium, nitrogen and iron). The primary abundances which best describe the Auger data were simulated through the Telescope Array (TA) Middle Drum (MD) fluorescence and surface detector array. The simulated events were analyzed by the TA Collaboration using the same procedure as applied to their data. The result is a simulated version of the Auger data as it would be observed by TA. This analysis allows a direct comparison of the evolution of Xmax\langle X_{\rm max} \rangle with energy of both data sets. The Xmax\langle X_{\rm max} \rangle measured by TA-MD is consistent with a preliminary simulation of the Auger data through the TA detector and the average difference between the two data sets was found to be (2.9±2.7  (stat.)±18  (syst.)) g/cm2(2.9 \pm 2.7\;(\text{stat.}) \pm 18\;(\text{syst.}))~\text{g/cm}^2.Comment: To appear in the Proceedings of the UHECR workshop, Springdale USA, 201

    Loss of Bim Increases T Cell Production and Function in Interleukin 7 Receptor–deficient Mice

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    Interleukin (IL)-7 receptor (R) signaling is essential for T and B lymphopoiesis by promoting proliferation, differentiation, and survival of cells. Mice lacking either IL-7 or the IL-7Rα chain have abnormally low numbers of immature as well as mature T and B lymphocytes. Transgenic expression of the apoptosis inhibitor Bcl-2 rescues T cell development and function in IL-7Rα–deficient mice, indicating that activation of a proapoptotic Bcl-2 family member causes death of immature and mature T cells. BH3-only proteins such as Bim, which are distant proapoptotic members of the Bcl-2 family, are essential initiators of programmed cell death and stress-induced apoptosis. We generated Bim/IL-7Rα double deficient mice and found that loss of Bim significantly increased thymocyte numbers, restored near normal numbers of mature T cells in the blood and spleen, and enhanced cytotoxic T cell responses to virus infection in IL-7Rα−/− mice. These results indicate that Bim cooperates with other proapoptotic proteins in the death of IL-7–deprived T cell progenitors in vivo, but is the major inducer of this pathway to apoptosis in mature T cells. This indicates that pharmacological inhibition of Bim function might be useful for boosting immune responses in immunodeficient patients

    Multiple Dendritic Cell Populations Activate CD4+ T Cells after Viral Stimulation

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    Dendritic cells (DC) are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8α DC play a prominent, and sometimes exclusive, role in driving amplification of CD8+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4+ and CD8+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8α DC populations in the amplification of CD8+ and CD4+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8+ T cells are dominated by presentation of antigen by CD8α DC but can involve non-CD8α DC. In contrast, CD4+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity
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