Coligation of the hepatitis C virus receptor CD81 with CD28 primes naive T lymphocytes to acquire type 2 effector function

Costimuli provide supplementary signals required by naive T cells to become fully activated upon Ag encounter. Tetraspanins are a large family of transmembrane proteins that can costimulate T cells when engaged in vitro. In this study, we describe for the first time that coligation of the tetraspanins CD81, CD82, or CD9 with the costimulatory molecule CD28 in vitro leads to proliferation of naive T cells. When activated through this pathway, both CD4+ and CD8+ naive T cells differentiate into type 2 effector cells, which produce IL-4, IL-5, IL-13, and IL-10, together with IL-2 and TNF-alpha, but little to no IFN-gamma. These effector cells descend from precursors that display early and strong production of IL-4, STAT6 phosphorylation, and up-regulation of the transcription factor GATA-3, suggesting a direct skewing toward Th2 differentiation without a Th0 intermediate. The hepatitis C virus envelope protein E2 is the only ligand known for CD81. Therefore, we propose that this new type of Ag-independent T cell activation may occur in hepatitis C virus-infected individuals, contributing to liver inflammation, impaired type 1 immune responses, and recurrent flares of type 2 immunity associated with chronic infection

Helicobacter pylori Induces Activation of Human Peripheral γδ+ T Lymphocytes

Helicobacter pylori is a Gram-negative bacterium that causes gastric and duodenal diseases in humans. Despite a robust antibody and cellular immune response, H. pylori infection persists chronically. To understand if and how H. pylori could modulate T cell activation, in the present study we investigated in vitro the interaction between H. pylori and human T lymphocytes freshly isolated from peripheral blood of H. pylori-negative donors. A direct interaction of live, but not killed bacteria with purified CD3+ T lymphocytes was observed by microscopy and confirmed by flow cytometry. Live H. pylori activated CD3+ T lymphocytes and predominantly γδ+ T cells bearing the TCR chain Vδ2. Upon interaction with H. pylori, these cells up-regulated the activation molecule CD69 and produced cytokines (such as TNFα, IFNγ) and chemokines (such as MIP-1β, RANTES) in a non-antigen-specific manner. This activation required viable H. pylori and was not exhibited by other Gram-negative bacteria. The cytotoxin-associated antigen-A (CagA), was at least partially responsible of this activation. Our results suggest that H. pylori can directly interact with T cells and modulate the response of γδ+ T cells, thereby favouring an inflammatory environment which can contribute to the chronic persistence of the bacteria and eventually to the gastric pathology

Queer In AI: A Case Study in Community-Led Participatory AI

Queerness and queer people face an uncertain future in the face of ever more widely deployed and invasive artificial intelligence (AI). These technologies have caused numerous harms to queer people, including privacy violations, censoring and downranking queer content, exposing queer people and spaces to harassment by making them hypervisible, deadnaming and outing queer people. More broadly, they have violated core tenets of queerness by classifying and controlling queer identities. In response to this, the queer community in AI has organized Queer in AI, a global, decentralized, volunteer-run grassroots organization that employs intersectional and community-led participatory design to build an inclusive and equitable AI future. In this paper, we present Queer in AI as a case study for community-led participatory design in AI. We examine how participatory design and intersectional tenets started and shaped this community’s programs over the years. We discuss different challenges that emerged in the process, look at ways this organization has fallen short of operationalizing participatory and intersectional principles, and then assess the organization’s impact. Queer in AI provides important lessons and insights for practitioners and theorists of participatory methods broadly through its rejection of hierarchy in favor of decentralization, success at building aid and programs by and for the queer community, and effort to change actors and institutions outside of the queer community. Finally, we theorize how communities like Queer in AI contribute to the participatory design in AI more broadly by fostering cultures of participation in AI, welcoming and empowering marginalized participants, critiquing poor or exploitative participatory practices, and bringing participation to institutions outside of individual research projects. Queer in AI’s work serves as a case study of grassroots activism and participatory methods within AI, demonstrating the potential of community-led participatory methods and intersectional praxis, while also providing challenges, case studies, and nuanced insights to researchers developing and using participatory methods

Hepatitis C Virus Protects Human B Lymphocytes from Fas-Mediated Apoptosis via E2-CD81 Engagement

HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production

Dependability assessment of ITER cask et plug remote handling system during nuclear maintenance operations

International audienceSince the ITER Casks will be not shielded, human access will be forbidden in trajectory zones and, in the event of failure of Cask and Plug Remote Handling System (CPRHS) functions, rescue operations will have to be remotely conducted. As potential failure modes could be severe in terms of time to repair, an inventory of CPRHS function outages and a risk analysis have been made at each stage of a diagnostic port plug maintenance process. CPRHS availability has been calculated in the framework of a RAMI analysis and the resulting time to perform the CPRHS operations for the maintenance of 2 Equatorial Port Plugs (EPP) has been confirmed by using a probabilistic Monte Carlo approach

Ionic liquids in methyltrioxorhenium catalyzed epoxidation-methanolysis of glycals under homogeneous and heterogeneous conditions

The efficient and high yielding domino epoxidation-methanolysis of glycals has been achieved under environment friendly conditions by oxidation with urea hydrogen peroxide adduct (UHP) and H2O2 in ionic liquids (ILs) catalyzed by methyltrioxorhenium and different heterogeneous methyltrioxorhenium derivatives. The facial diastereoselectivity of the oxidation ranged from satisfactory to excellent ones depending on the substrate and could be optimized by ample screening of catalysts. The oxidations performed with UHP proceeded with a higher degree of diastereoselectivity than those performed with H2O2. High yields of products and conversions of substrates were obtained under mild experimental conditions and by the use of simple work-up procedures. © 2008 Elsevier B.V. All rights reserved

ITER transfer cask: Preliminary assessment of dose rate due to dust remained in the cask

International audienceThe Remote Handling tasks scheduled during the ITER maintenance shutdown require transportation of in-vessel components and remote-handling tools from the Vacuum Vessel (VV) ports to the Hot Cell Building (HCB). These components and tools will be moved using the Cask and Plug Remote Handling System (CPRHS). During plasma operations, plasma facing components will be highly activated by neutrons and/or contaminated with tritium. After plasma operations, activated dust will be removed from the VV but some amounts will remain. Therefore, the CPRHS may be contaminated by residual activated dust due to the transportation of these components between the VV and the HCB. As the CPRHS is not shielded, residual activated dust may lead to a residual dose rate around the CPRHS. To assess the risk of external exposition in case of human intervention for maintenance purpose inside or close to the CPRHS, dose rate estimations were performed around and inside the CPRHS for several initial dust configurations with the normalized value of 1 g of residual activated dust. The results of this study constitute a dosimetric data base and may support ITER Organization in the definition of a decontamination level and maintenance plan