bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate Social Responsibility (CSR) as a People Caring Concept
Authors: Athanasopoulou Pinelopi
Published: April 2014

CSR has been a widely-researched concept during the last three decades. However, there is no agreement on its definition or its dimensions; antecedents and consequences and there is no comprehensive model for its analysis. The origins of CSR lie in philanthropy and the highest level of CSR is considered to involve philanthropic actions. CSR is a people-caring concept that is incorporated in firms' strategy. Strategic CSR is based on stakeholder theory and is used to provide competitive advantages through product or brand differentiation. Although there have been many efforts to measure the effectiveness of CSR, there is no single way of assessing CSR performance. Also, effective CSR communication is a very important matter for firms and although there is a lot of research on this subject, the debate is still on regarding what to say; through which channels, and how to say it in order to avoid consumer scepticism and reap strategic benefits. Based on this analysis, emergent themes of research are identified in this chapter and areas of further research are proposed.
The Evolution of Consumerism in the Marketing Education
Authors: Spais George S.
Published: April 2014

The chapter examines how consumerism- one of the primary key themes in marketing and business courses- has evolved the last decade and envisages the shape of these set of courses in the future. From the 1,935 words for 20 key-concepts counted in 141 online course descriptions in English of the last 10 periods delivered by Business and Management Schools or Business/Marketing Academic Depts. of 88 Universities and Colleges, “Marketing,” “business,” “ethics” and “social responsibility” were included in 100% of the course descriptions analyzed, indicating their coverage by all courses. In order to investigate the five (5) research objectives, HCA was adopted for an exploratory analysis based on single-linkage clustering method to reveal natural groupings of the key concepts within a data set of word counts that were not apparent and then multiple linear regression analyses were conducted. The trend analyses indicated prospects for the increasing focus around specific topics. The interpretation of the research results based on the assumptions of Mezirow's critical reflection provided very strong recommendations.
Green Marketing Strategy
Authors: Ahmad A F Wazir , Panni Mohammad Fateh Ali Khan
Published: April 2014

Within the campus of business ethics and social responsibility, green marketing strategy has become a much discussed issue in today's academic world as well as in the profession. Though corporate greening has gained a widespread recognition, different studies have found the concept still facing much confusion especially on norms of ideal green marketing practices. As a consequence, many organizations which are professing green marketing are not profound about it. Among those firms some are partially involved while some are not yet convinced to adopt the green marketing strategy mostly because they do not find it worthwhile regarding revenue and profit. In academia, there are considerable amount of literature providing scattered individual insights from different perspectives. A chapter synthesizing these literatures can be helpful for both academics and marketing practitioners. This chapter attempts to review the literature to understand the origin and evolution of green marketing and green marketing strategy with all its major fundamental dimensions. Based on the existing mainstream literature, the chapter also reveals the green marketing strategy from the strategic consumer behavioral perspective. Furthermore, it summarizes the key success factors behind green marketing, its impact on the organizational performance as well as recommendations for successful implementations. The chapter is a synthesis of the green marketing philosophy and green marketing strategy that might serve as an extensive reference material to both the researchers and marketing practitioners in conducting interesting future research in the field as well as in formulating and adopting appropriate green marketing strategies.
The Meaning of Consumption
Authors: Smith Terry
Published: April 2014

The “un-contestable hegemony of consumer capitalism” (Gabriel & Lang, 2006, p. 2) as the prevailing ideology of our times locates it as the primary creator and driver of production, competition, innovation, value and, latterly, values. In 1995, Miller recognised that “consumption, rather than production, was the vanguard of history” (p. 1). In that same year, the United Nations issued alarming statistics highlighting the influence of marketing on materialism and the fact that inequality in consumption was far wider than expected, severely undermining the environmental resource base. The backdrop of social theory and political economy within which consumerism and consumption are framed is a fragmented and complex one which has an unstable nature influenced by a range of complicated macro environmental factors. It is a postmodern landscape characterised by an all-pervasive consumer culture, the imperative of consumer rights and the use of consumption as a source of meaning. This chapter attempts to present a critical examination of the dominant academic, political, cultural and ecological discourses which constitute and contribute to this debate. At the epicentre is a post-modern dilemma about the delusion of choice, the illusion of freedom and the imperative of control - shifting priority from conspicuous consumption to conscientious conscience consumption.
Predicting Behavioral Intentions Toward Sustainable Fashion Consumption
Authors: Manchiraju Srikant
Published: April 2014

In recent years, sustainable consumption has received considerable attention. In fact, to save the planet Earth and future generations, it has been proposed the issue of sustainable consumption should be addressed. Consequently, in the present chapter, two theoretical models are analyzed separately, as well as in conjunction, to understand sustainable consumption in the context of fashion. Furthermore, the present study's theoretical and managerial implications are discussed.
Consumer Confidence in Responsible Tourism
Authors: Manente Mara , Minghetti Valeria , Mingotto Erica , Casarin Francesco
Published: April 2014

The chapter focuses on reporting systems which assess responsible tourism and Corporate Social responsibility (CSR) in the tourism industry. These tools have recently received more and more attention from the international academic and professional community, given the urgent need to promote a socially, environmentally and economically sustainable development of tourism. The use of reporting systems can encourage responsible practices by tourism businesses, improving internal processes and activities along the tourism value chain, as well as enhance consumer confidence in respectful companies and in responsible tourism. Through the application of the Analytic Hierarchy Process (AHP), the chapter develops a critical assessment of the reporting systems currently available in Europe, in order to support the diffusion of responsible policies and practices in the tourism industry and the businesses' commitment towards clients. Particular attention is paid to small and medium-size tourism enterprises, since they have more difficulties in organising their business according to social and ecological principles and to develop the conditions under which a product can be defined as “responsible”. The analysis underlines that the evaluation of these tools, in terms of their effectiveness and reliability in monitoring business responsibility, depends on the criteria taken into account for the analysis and then on the auditors' selection of appropriate variables.
The Psychology of Consumerism in Business and Marketing
Authors: Tran Ben
Published: April 2014

In the past decade or so, various models have emerged concerning the study of culture and marketing in regards to consumerism, of which Geert Hofstede's dimensional model of national culture has been applied to various areas of global branding and advertising, and the underlying theories of consumer behavior. Hofstede's model has been used to explain differences regarding the concepts of self, personality and identity, which in turn explain variations in branding strategy and communications. Thus, the purpose of this chapter is to address the psychology of consumerism in business and marketing from the macro and micro behaviors of Hofstede's cultural consumers. The chapter emphasizes Hofstede's fifth cultural dimension, long-term versus short-term orientation regarding marketing. In so doing, both macro and micro paradigms on the psychology of consumers' behaviors will be covered in relation to marketing, as well as a brief history of marketing and the marketing field.
Consumption, Anti-Consumption and Consumption Communities
Authors: Loureiro Sandra Maria Correia , Pires Ana Regina , Cayolla Ricardo
Published: April 2014

Broadly, consumerism can be considered as a set of beliefs and values integrated into, but not exclusive to, the global market system, intended to make people believe that happiness is best achieved through possessions. In literature there are several other definitions of consumerism, consumption, anti-consumption and consumption communities. Therefore, the purpose of this chapter is to (i) present an overview of the research concepts, models and main theories of this topic, based on a systematic literature review and using the following databases to search information: Elsevier, Emerald, Science Direct, EBSCO, Springer, and ISI web knowledge; (ii) formulate a framework of consumption waves and anti-consumption motivations and types (iii) discuss consumption and anti-consumerism in football (soccer) context. The current study also carried out semi-structured interviews with 15 football fans with an average duration of 60 minutes each. Findings revealed four main types of anti-consumption: Global impact consumers or anti-consumption society; Selective consumption or anti-loyalists market activists; Conservative or Simplifiers; and Rejection of brand hegemony. Football fans are avid consumers of many products, such as information, knowledge, travels, tickets to matches, and diverse merchandizing from brands that sponsor the team and the club. Nevertheless, they are also selective consumers, rejecting everything connected to the rival clubs. Finally, the chapter provides insights for further research and managerial implications. In this vein, this chapter contributes to the existing literature giving insights for a better understanding of football clubs and fans as consumers and anti-consumers.
Linking Effective Whole Life Cycle Cost Data Requirements to Parametric Building Information Models Using BIM Technologies
Authors: Kehily Dermot , Woods Trevor , McDonnell Fiacra
Published: April 2014

This paper demonstrates the capabilities of BIM (Building Information Modeling) in leveraging Whole Life Cycle Cost (WLCC) data requirements to perform WLCC calculations and produce WLLC estimates. The research determines the extent to which WLCC data, such as time, interest rates, escalation rates and real costs can be attached to parametric BIM data to be used effectively to create speedier and more accurate real-time WLLC analysis. Without incorporating WLCC data in the BIM, a complete picture of a construction project's WLCC cannot be formed from the default outputs of the model. BIM 5D applications such as CostX utilise the parametric properties of the model, providing users with the ability to generate information and quantities from the BIM to be used in a formatted cost plan. The benefit of the 5D process is that selected quantity surveying information in the BIM can be live linked from the model to the cost plan providing a real-time analysis of WLLC. The authors demonstrate in this paper how they leverage BIM, by incorporating WLCC data and calculations in a customised CostX workbook, thus providing the authors with the ability to live link the output values from the model to the values in the workbook to perform WLCC. This paper demonstrates the practical application of this process on a pilot project in order to complete a WLCC analysis.
Case Study
Authors: Tabrizi Aydin , Sanguinetti Paola
Published: April 2014

This case study focuses on the operational performance of a Leadership in Energy & Environmental Design (LEED)-rated building with the application of Building Information Modeling (BIM) to evaluate its capacity to achieve Zero Net Energy (ZNE). Retrofit options for renewable energy implementation are examined in conjunction with scenarios of building operation. In this study, two different BIM processes have been conducted for the energy modeling: object-oriented geometric information modeling (e.g., envelope, doors, windows, walls, zones, etc.) with a BIM tool and energy modeling (e.g., materials, heat resistance, location, weather data, renewables, etc.) with an energy simulation tool. The simulation model is compared to the real building performance and alternative renewable energy scenarios are evaluated. The results are used to make recommendations for the optimization of building performance and consideration of energy-efficient strategies for building performance enhancement. The research points to discontinuities between photovoltaic panel degradation over time and the LEED credit.
A New Sensor-Based Spatial OLAP Architecture Centered on an Agricultural Farm Energy-Use Diagnosis Tool
Authors: Bimonte Sandro , Pradel Marilys , Boffety Daniel , Tailleur Aurelie , André Géraldine , Bzikha Rabi , Chanet Jean-Pierre
Published: April 2014

Agricultural energy consumption is an important environmental and social issue. Several diagnosis tools have been proposed to define indicators for analyzing the large-scale energy consumption of agricultural farm activities (year, farm, production activity, etc.). In Bimonte, Boulil, Chanet and Pradel (2012), the authors define (i) new appropriate indicators to analyze agricultural farm energy-use performance on a detailed scale and (ii) show how Spatial Data Warehouse (SDW) and Spatial OnLine Analytical Processing (SOLAP) GeoBusiness Intelligence (GeoBI) technologies can be used to represent, store, and analyze these indicators by simultaneously producing graphical and cartographic reports. These GeoBI technologies allow for the analysis of huge volumes of georeferenced data by providing aggregated numerical values visualized by means of interactive tabular, graphical, and cartographic displays. However, existing data collection systems based on sensors are not well adapted for agricultural data. In this paper, the authors show the global architecture of our GeoBI solution and highlight the data collection process based on agricultural ad hoc sensor networks, the associated transformation and cleaning operations performed by means of Spatial Extract Transform Load (ETL) tools, and a new implementation of the system using a web-services-based loosely coupled SOLAP architecture to provide interoperability and reusability of the complex multi-tier GeoBI architecture. Moreover, the authors detail how the energy-use diagnosis tool proposed in Bimonte, Boulil, Chanet and Pradel (2012) theoretically fits with the sensor data and the SOLAP approach.
Collective Threshold Model Based on Utility and Psychological Theories
Authors: Li Zhenpeng , Tang Xijin
Published: April 2014

In this paper the authors investigate critical phase transition characteristic of collective action by considering the mechanisms of both rational utility and psychological threshold based on the Granovetter (1978)'s threshold model. Numeric simulation is used to observe the collective dynamics with consideration of both spatial factor and social network friendship density. The authors observe that activation threshold model with both utility and psychological thresholds included shows more stable in phase transition than that in the classic model. The authors also find that spatial factor and friendship network density have trivial impact on final equilibrium of collective behavior.
Preparation and Characterization of Polyacrylonitrile in Aqueous Slurry Polymerization
Authors: Lou Ben Lin , Li Yuan Yuan , Xiao Ru
Published: April 2014

Polyacrylonitrile (PAN) is widely used for its superior properties, and comonomers are usually introduced to improve its properties. In this paper, 2-acrylamide-2-methylpropanesulfonic acid (AMPS) and acrylamide (AM) were used as comonomers to prepare polyacrylonitrile by aqueous slurry polymerization. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) was used to characterize the chemical structures, the thermal properties, degree of crystallinity of polyacrylonitrile copolymer. The results show that the best thermal property of AN/AMPS/AM ternary copolymer in cyclization reaction was achieved in the proportion (w/w/w) 98/1/1. The exothermic quantity of AN/AMPS/AM ternary copolymer is 612.1 J/g while that of PAN homopolymer is 519.5 J/g during the cyclization reaction, carried out in DSC under nitrogen atmosphere. The introduction of AMPS and AM has small impact on the degree of crystallinity of PAN, the degree of crystallinity approximates 53.8%
Investigation of Morphology and Electrical Properties of Contact Materials after Airtightness Test
Authors: Kong Zhi Gang , Kong Yi Gang
Published: April 2014

In this article, the corrosion behavior of the gold plating and the silver plating specimens are studied. It is found that the airtightness have effects on the contact properties of the different plating specimens. The surface morphology of specimens is observed by stereoscopic microscope and scanning electron microscope (SEM). Chemical constitution was examined by X-ray energy spectrum. The contact resistances were measured by four-point method. The experiment results show that the corrosion appearance of the silver plating is severer than that of the gold plating one after airtightness test. The corrosion degree of plating specimens decreased with the increase of the coatings thickness. The static contact resistances of corrosive spots appear higher contact resistance than normal value. It is found the high and unstable contact resistance of the corrosion products is more likely to cause contact failure. The influencing factor of the corrosion products with different plating has an important influence on the airtightness test and the contact failure of electric connector.
Effect of Two Heat Treatment Processes on Microstructures and Tensile Behaviors of Ni-Based Superalloy K465
Authors: Gu Yu Li , Tao Chun Hu , Li Nan , Wei Zhen Wei , Liu Pu
Published: April 2014

The effect of two heat treatment processes on microstructures and tensile behaviors of K465 superalloy was investigated and compared. The results show that hot isostatic pressing (HIP) process partly or completely eliminated the micro-porosity to densify K465 alloy, and can effectively reduce the size of γ′ phase and improve the tensile strength and plasticity of K465 alloy. Electron probe micro-analysis (EPMA) studies revealed that the element segregation ratio was smaller in the HIP process alloy than that in the ordinary process alloy. nanoindentation tests revealed that elastic modulus and the hardness in the interdendrite of K465 alloy for HIP process were higher than that for the ordinary process.
Cutting Edge: Depletion of CD4+CD25+ Regulatory T Cells Is Necessary, But Not Sufficient, for Induction of Organ-Specific Autoimmune Disease
Authors: McHugh Rebecca S. , Shevach Ethan M.
Published: April 2014

Thymectomy of BALB/c mice on day 3 of life results in the development of autoimmune gastritis (AIG) due to the absence of CD4+CD25+ regulatory T cells. However, depletion of CD4+CD25+ T cells by treatment with anti-CD25 rarely resulted in AIG. Depletion was efficient, as transfer of splenocytes from depleted mice induced AIG in nu/nu mice. One explanation for this result is that CD4+CD25− T cells upon transfer to nude recipients undergo lymphopenia-induced proliferation, providing a signal for T cell activation. Cotransfer of CD25+ T cells did not inhibit initial proliferation but did suppress AIG. Surprisingly, immunization with the AIG target Ag, H/K ATPase, in IFA failed to induce disease in normal animals but induced severe AIG in CD25-depleted mice. These results demonstrate that second signals (nonspecific proliferation, TCR activation, or inflammation) are needed for induction of autoimmunity in the absence of CD25+ regulatory T cells.
Cutting Edge: BLyS Enables Survival of Transitional and Mature B Cells Through Distinct Mediators
Authors: Hsu Benjamin L. , Harless Susan M. , Lindsley R. Coleman , Hilbert David M. , Cancro Michael P.
Published: April 2014

These studies characterize BLyS responsiveness and receptor expression among transitional and mature peripheral B cells. The results show a maturation-associated increase in BLyS binding capacity that reflects differential expression patterns of the three BLyS receptors. Accordingly, BLyS administration enlarges only late transitional and mature peripheral B (MB) cell compartments. Furthermore, bromodeoxyuridine labeling and cell cycle analyses show these effects are mediated through enhanced proportional survival of cells traversing the T2, T3, and MB cell stages, rather than by causing proliferation or slowing transit within these subsets. Despite similar effects on survival, BLyS up-regulates the antiapoptotic genes A1and bcl-xL in MB cells but not immature B cells. Together, these findings show that, while BLyS influences B cell survival in several peripheral differentiation subsets, the downstream mediators differ, thus providing the first direct evidence for an established B lineage survival system whose intermediates change as B cells mature.
Cutting Edge: MyD88 Is Required for Resistance toToxoplasma gondiiInfection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells
Authors: Scanga Charles A. , Aliberti Julio , Jankovic Dragana , Tilloy Florence , Bennouna Soumaya , Denkers Eric Y. , Medzhitov Ruslan , Sher Alan
Published: April 2014

Host resistance to the intracellular protozoan Toxoplasma gondii is highly dependent on early IL-12 production by APC. We demonstrate here that both host resistance and T. gondii-induced IL-12 production are dramatically reduced in mice lacking the adaptor molecule MyD88, an important signaling element used by Toll-like receptor (TLR) family members. Infection of MyD88-deficient mice with T. gondii resulted in uncontrolled parasite replication and greatly reduced plasma IL-12 levels. Defective IL-12 responses to T. gondii Ags (soluble tachyzoite Ag (STAg)) were observed in MyD88−/− peritoneal macrophages, neutrophils, and splenic dendritic cells (DC). In contrast, DC from TLR2- or TLR4-deficient animals developed normal IL-12 responses to STAg. In vivo treatment with pertussis toxin abolished the residual IL-12 response displayed by STAg-stimulated DC from MyD88−/− mice. Taken together, these data suggest that the induction of IL-12 by T. gondii depends on a unique mechanism involving both MyD88 and G protein-coupled signaling pathways.
Cutting Edge: Vα14-Jα281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice
Authors: Mars Lennart T. , Laloux Véronique , Goude Karine , Desbois Sabine , Saoudi Abdelhadi , Van Kaer Luc , Lassmann Hans , Herbelin André , Lehuen Agnès , Liblau Roland S.
Published: April 2014

Although deficiencies in the NKT cell population have been observed in multiple sclerosis and mouse strains susceptible to experimental autoimmune encephalomyelitis (EAE), little is known about the function of these cells in CNS autoimmunity. In this work we report that TCR Vα14-Jα281 transgenic nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are protected from EAE. The protection is associated with a striking inhibition of Ag-specific IFN-γ production in the spleen, implying modulation of the encephalitogenic Th1 response. This modulation is independent of IL-4 because IL-4-deficient Vα14-Jα281 mice are still protected against EAE and independent of NKT cell-driven Th1 to Th2 deviation, because no increased autoantigen-specific Th2 response was observed in immunized Vα14-Jα281 transgenic mice. Our findings indicate that enrichment and/or stimulation of CD1d-dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity.
T and B Cell Recovery in Arthritis Adoptively Transferred to SCID Mice: Antigen-Specific Activation Is Required for Restoration of Autopathogenic CD4+ Th1 Cells in a Syngeneic System
Authors: Bárdos Tamás , Mikecz Katalin , Finnegan Alison , Zhang Jian , Glant Tibor T.
Published: April 2014

T cell homeostasis is a physiological function of the immune system that maintains a balance in the numbers and ratios of T cells at the periphery. A self-MHC/self-peptide ligand can induce weak (covert) signals via the TCR, thus providing an extended lifespan for naive T cells. A similar mechanism is responsible for the restoration of immune homeostasis in severe lymphopenic conditions such as those following irradiation or chemotherapy, or upon transfer of lymphocytes to nu/nu or SCID mice. To date, the genetic backgrounds of donor and recipient SCID mice were unmatched in all autoimmune arthritis transfer experiments, and the recovery of lymphoid cells in the host has not been followed. In this study, we present the adoptive transfer of proteoglycan (PG)-induced arthritis using unseparated and T or B cell-depleted lymphocytes from arthritic BALB/c donors to genetically matched syngeneic SCID recipient mice. We demonstrate that selectively recovered lymphoid subsets determine the clinical and immunological status of the recipient. We found that when T cells were depleted (>98% depleted), B cells did not produce PG-specific anti-mouse (auto) Abs unless SCID mice received a second Ag (PG) injection, which promoted the recovery of Ag-specific CD4+ Th1 cells. Reciprocally, as a result of B cell recovery, high levels of serum anti-PG Abs were found in SCID mice that received B cell-depleted (>99% depleted) T lymphocytes. Our results indicate a selective and highly effective cooperation between CD4+ T cells and B lymphocytes that is required for the restoration of pathological homeostasis and development of autoimmune arthritis in SCID mice.
Dynamic Regulation of T Cell Immunity by CD43
Authors: Onami Thandi M. , Harrington Laurie E. , Williams Matthew A. , Galvan Marisa , Larsen Christian P. , Pearson Thomas C. , Manjunath N. , Baum Linda G. , Pearce Brad D. , Ahmed Rafi
Published: April 2014

During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43−/− mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from −/− mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific CD8 T cell response in vivo but plays a more significant role in trafficking of CD8 T cells to tissues such as the brain. More interestingly, CD43 plays a role in the contraction of the immune response, with CD43−/− mice showing increased numbers of Ag-specific CD8 T cells following initial expansion. Following the peak of expansion, Ag-specific CD8 T cells from −/− mice show similar proliferation but demonstrate increased Bcl-2 levels and decreased apoptosis of Ag-specific effector CD8 T cells in vitro. Consistent with a delay in the down-modulation of the immune response, following chronic viral infection CD43−/− mice show increased morbidity. These data suggest a dynamic role of CD43 during an immune response: a positive regulatory role in costimulation and trafficking of T cells to the CNS and a negative regulatory role in the down-modulation of an immune response.
Antiviral Immune Responses in the Absence of Organized Lymphoid T Cell Zones inplt/pltMice
Authors: Junt Tobias , Nakano Hideki , Dumrese Tilman , Kakiuchi Terutaka , Odermatt Bernhard , Zinkernagel Rolf M. , Hengartner Hans , Ludewig Burkhard
Published: April 2014

The paucity of lymph node (LN) T cells (plt) mutation in mice results in strongly reduced T cell numbers in LNs and homing defects of both dendritic cells (DCs) and naive T cells. In this study, we investigated the functional significance of the plt phenotype for the generation of antiviral immune responses against cytopathic and noncytopathic viruses. We found that DC-CD8+ T cell contacts and the initial priming of virus-specific T cells in plt/plt mice occurred mainly in the marginal zone of the spleen and in the superficial cortex of LNs. The magnitude of the initial response and the maintenance of protective memory responses in plt/plt mice was only slightly reduced compared with plt/+ controls. Furthermore, plt/plt mice mounted rapid neutralizing antiviral B cell responses and displayed normal Ig class switch. Our data indicate that the defective homing of DCs and naive T cells resulting from the plt/plt mutation results in a small, but not significant, effect on the induction of protective antiviral T and B cell immunity. Overall, we conclude that the spatial organization of secondary lymphoid T cell zones via the CCR7-CC chemokine ligand 19/CC chemokine ligand 21 pathway is not an absolute requirement for the initial priming and the maintenance of protective antiviral T and B cell responses.
CD36 or αvβ3 and αvβ5 Integrins Are Not Essential for MHC Class I Cross-Presentation of Cell-Associated Antigen by CD8α+ Murine Dendritic Cells
Authors: Schulz Oliver , Pennington Daniel J. , Hodivala-Dilke Kairbaan , Febbraio Maria , Reis e Sousa Caetano
Published: April 2014

Cross-presentation of cell-associated Ag is thought to involve receptor-mediated uptake of apoptotic cells by dendritic cells (DC), and studies with human DC strongly implicate the endocytic receptor CD36 and the integrins αvβ3 and/or αvβ5 in this process. In the mouse, cross-presentation was recently shown to be a function of CD8α+ DC. Here we report that CD36 is expressed on CD8α+, but not on CD8α−, DC. To address the role of CD36 in cross-presentation we compared CD36−/− and CD36+/+ H-2b DC for their ability to stimulate naive OT-1 T cells specific for OVA plus H-2Kb in the presence of OVA-loaded MHC-mismatched splenocytes as a source of cell-associated Ag for cross-presentation. Surprisingly, no difference was seen between CD36−/− and CD36+/+ CD8α+ DC in their ability to cross-present cell-associated OVA or to capture OVA-bearing cells. Furthermore, the proliferation of CFSE-labeled OT-1 cells in response to OVA cross-presentation in vivo was normal in CD36−/− bone marrow chimeras, also arguing against a necessary role for CD36 in cross-presentation by DC or other APC. DC doubly deficient for β3 and β5 integrins were similarly unimpaired in their ability to cross-present OVA-bearing cells in vitro. These data demonstrate that in the mouse, receptors other than CD36 or β3 and β5 integrins can support the specialized cross-presenting function of CD8α+ DC.
Apoptosis Mediated Through CD45 Is Independent of Its Phosphatase Activity and Association with Leukocyte Phosphatase-Associated Phosphoprotein
Authors: Fortin Marylène , Steff Ann-Muriel , Felberg Jackie , Ding Isabelle , Schraven Burkhart , Johnson Pauline , Hugo Patrice
Published: April 2014

Besides the well-recognized role of CD45 as a major player in TCR signaling, we and others have demonstrated that cross-linking of CD45 with mAbs can induce cell death in T lymphocytes. To investigate the role of CD45 phosphatase activity in apoptosis induction, we expressed either wild-type or phosphatase-dead CD45 molecules in a CD45-deficient BW5147 T cell line. We show here that the phosphatase activity of CD45 was not required for apoptosis triggering after cross-linking of the molecule. It is noteworthy that a revertant of the CD45-negative BW5147 cell line, expressing a truncated form of CD45 lacking most of the cytoplasmic domain, was also susceptible to CD45-mediated death. Moreover, we also demonstrate that leukocyte phosphatase-associated phosphoprotein expression is totally dispensable for CD45-mediated apoptosis to occur. Taken together, these results strongly suggest a role for the extracellular and/or the transmembrane portion of CD45 in apoptosis signaling, which contrasts with the previously reported functions for CD45 in T lymphocytes.
IL-2 and IL-12 Alter NK Cell Responsiveness to IFN-γ-Inducible Protein 10 by Down-Regulating CXCR3 Expression
Authors: Hodge Deborah L. , Schill William B. , Wang Ji Ming , Blanca Isaac , Reynolds Della A. , Ortaldo John R. , Young Howard A.
Published: April 2014

Cytokine treatment of NK cells results in alterations in multiple cellular responses that include cytotoxicity, cytokine production, proliferation, and chemotaxis. To understand the molecular mechanisms underlying these responses, microarray analysis was performed and the resulting gene expression patterns were compared between unstimulated, IL-2, IL-2 plus IL-12, and IL-2 plus IL-18-stimulated NK92 cells. RNase protection assays and RT-PCR confirmed microarray predictions for changes in mRNA expression for nine genes involved in cell cycle progression, signal transduction, transcriptional activation, and chemotaxis. Multiprobe RNase protection assay also detected changes in the expression of CCR2 mRNA, a gene that was not imprinted on the microarray. We subsequently expanded our search for other chemokine receptor genes absent from the microarray and found an IL-2- and IL-12-dependent decrease in CXCR3 receptor mRNA expression in NK92 cells. A detailed analysis of CXCR3 expression in primary NK cells revealed that an IL-2 and an IL-12 together significantly decreased the CXCR3 receptor mRNA and receptor surface expression by 6 and 24 h of treatment, respectively. This decrease in receptor expression was associated with a significant reduction in chemotaxis in the presence of IFN-γ-inducible protein-10. The decline in CXCR3 mRNA was due to transcriptional and posttranscriptional mechanisms as the addition of actinomycin D to IL-2- and IL-12-treated NK92 slightly altered the half-life of the CXCR3 mRNA. Collectively, these data suggest that IL-2 and IL-12 directly affect NK cell migratory ability by rapid and direct down-regulation of chemokine receptor mRNA expression.
CD4-Lck Through TCR and in the Absence of Vav Exchange Factor Induces Bax Increase and Mitochondrial Damage
Authors: Tuosto Loretta , Marinari Barbara , Piccolella Enza
Published: April 2014

In the present study, we aimed to demonstrate that CD4 may represent a critical turning point that governs the apoptotic and survival programs in T cells, without modifying the physical association with the TCR-CD3 complex. To address this issue, we have explored the possibility that the activation of CD4 may transduce apoptotic signals unless signaling effectors neutralize them. Our data show that in Jurkat T cells CD4 engagement by Leu3a mAb results in a rapid and strong increase of Lck kinase activity, subsequent alterations of mitochondrial membrane potential, and apoptosis. Critical parameters are coassociation of CD4/Lck with TCR/CD3 and up-regulation of the proapoptotic protein Bax. Indeed, Leu3a-mediated Lck activation failed to induce apoptotic features in Jurkat cells either defective for TCR/CD3 or overexpressing the antiapoptotic protein Bcl-2. Furthermore, we demonstrate that Leu3a treatment of Jurkat cells overexpressing Vav results in the inhibition of mitochondrial damage and apoptosis; this rescue effect is accompanied with a significant decrease of Bax expression observed in apoptotic cells. Our evidence that the activation of Lck activates in T cells apoptotic pathways which are counteracted by Vav, a signaling molecule that cooperates with CD28 to boost TCR signals, suggests a novel role for costimulation in protecting T cells from CD4-mediated cell death.
Early Antigen-Specific Response by Naive CD8 T Cells Is Not Altered with Aging
Authors: Li Shaokang P. , Cai Zeling , Shi Weixing , Brunmark Anders , Jackson Michael , Linton Phyllis-Jean
Published: April 2014

Both a dramatic decline in CD8 responses and a switch to memory T cell predominance occur with aging. The extent to which the loss of responsiveness is the consequence of the accumulation of more differentiated vs intrinsically defective T cells (or both) has been unclear. Using similar conditions of Ag stimulation, we have examined the responses generated by CD8+ cells isolated from aged TCR transgenic mice. We found that the naive transgene+ CD8+ cells from aged 2C mice expressed activation markers, produced IL-2, proliferated, and differentiated into cytotoxic T cells as efficiently as their young counterparts. The extent of responsiveness and the level of the responses were comparable in both age groups regardless of the stimulatory conditions used, i.e., partial costimulation/adhesion molecule expression on APCs, or presentation of lower affinity peptide or diminished peptide concentrations. By day 4 after Ag stimulation, no significant age-related differences were observed in the number of effector cells generated nor in the levels of secreted IL-2 or IFN-γ. Upon restimulation of effector cells, IL-2 secretion and to a lesser extent TNF-α expression, but not IFN-γ secretion, were diminished with age. These findings suggest that age-associated alterations in naive CD8 cell function are not found after primary stimulation, but may become apparent upon restimulation.
Lipopolysaccharide- and Lipoteichoic Acid-Induced Tolerance and Cross-Tolerance: Distinct Alterations in IL-1 Receptor-Associated Kinase
Authors: Jacinto Randy , Hartung Thomas , McCall Charles , Li Liwu
Published: April 2014

Human Toll-like receptor (TLR) 4 and TLR2 receptors recognize LPS or lipoteichoic acid (LTA), respectively. Prolonged exposure of human macrophages/monocytes to bacterial LPS induces a state of adaptation/tolerance to subsequent LPS challenge. Inflammatory gene expressions such as IL-1β and TNF-α are selectively repressed, while certain anti-inflammatory genes such as secretory IL-1R antagonist are still induced in LPS-adapted/tolerant cells. In this report, we demonstrate that LPS-tolerized human promonocytic THP-1 cells develop cross-tolerance and no longer respond to LTA-induced IL-1β/TNF-α production, indicating that disruption of common intracellular signaling is responsible for the decreased IL-1β/TNF-α production. We observe that down-regulation of IL-1R-associated kinase (IRAK) protein level and kinase activity closely correlates with the development of cross-tolerance. IRAK protein levels and kinase activities in LPS-tolerized cells remain low and hyporesponsive to subsequent LPS or LTA challenges. We also demonstrate that THP-1 cells with prolonged LTA treatment develop LTA tolerance and do not express IL-1β/TNF-α upon further LTA challenge. Strikingly, cells tolerized with LTA are only refractory to subsequent LTA challenge and can still respond to LPS stimulation. Correspondingly, stimulation of TLR2 by LTA, although activating IRAK, does not cause IRAK degradation. IRAK from LTA-tolerized cells can be subsequently activated and degraded by further LPS challenge, but not LTA treatment. Our studies reveal that LTA-induced tolerance is distinct compared with that of LPS tolerance, and is likely due to disruption of unique TLR2 signaling components upstream of MyD88/IRAK.
Role of IFN-γ in Th1 Differentiation: IFN-γ Regulates IL-18Rα Expression by Preventing the Negative Effects of IL-4 and by Inducing/Maintaining IL-12 Receptor β2 Expression
Authors: Smeltz Ronald B. , Chen June , Ehrhardt Rolf , Shevach Ethan M.
Published: April 2014

Two key events occur during the differentiation of IFN-γ-secreting Th1 cells: up-regulation of IL-12Rβ2 and IL-12-driven up-regulation of IL-18Rα. We previously demonstrated that IL-12-driven up-regulation of IL-18Rα expression is severely impaired in IFN-γ−/− mice. However, it was unclear from these studies how IFN-γ influenced IL-18Rα since IFN-γ alone had no direct effect on IL-18Rα expression. In the absence of IL-4, IL-12-dependent up-regulation of IL-18Rα/IL-12Rβ2 was independent of IFN-γ. However, in the presence of IL-4, IFN-γ functions to limit the negative effects of IL-4 on both IL-18Rα and IL-12Rβ2. Neutralization of IL-4 restored IL-12-driven up-regulation of IL-18Rα/IL-12Rβ2 in an IFN-γ-independent fashion. In the absence of both IL-12 and IL-4, IFN-γ up-regulates IL-12β2 expression and primes IFN-γ-producing Th1 cells. When T cells were primed in the presence of IL-4, no correlation was found between the levels of expression of the IL-18Rα or the IL-12Rβ2 and the capacity of these cells to produce IFN-γ, suggesting that IL-4 may also negatively affect IL-12-mediated signal transduction and thus Th1 differentiation. These data clarify the role of IFN-γ in regulation of IL-18Rα/IL-12Rβ2 during both IL-12-dependent and IL-12-independent Th1 differentiation.
Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression
Authors: Nishimura Miyuki , Umehara Hisanori , Nakayama Takashi , Yoneda Osamu , Hieshima Kunio , Kakizaki Mayumi , Dohmae Naochika , Yoshie Osamu , Imai Toshio
Published: April 2014

Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell adhesion and cell migration. Here we show that CX3CR1 defines peripheral blood cytotoxic effector lymphocytes commonly armed with intracellular perforin and granzyme B, which include NK cells, γδ T cells, and terminally differentiated CD8+ T cells. In addition, soluble fractalkine preferentially induced migration of cytotoxic effector lymphocytes. Furthermore, interaction of cytotoxic effector lymphocytes with membrane-bound fractalkine promoted subsequent migration to the secondary chemokines, such as macrophage inflammatory protein-1β/CC ligand 4 or IL-8/CXC ligand 8. Thus, fractalkine expressed on inflamed endothelium may function as a vascular regulator for cytotoxic effector lymphocytes, regardless of their lineage and mode of target cell recognition, through its ability to capture them from blood flow and to promote their emigration in response to other chemokines.
A Decaepitope Polypeptide Primes for Multiple CD8+ IFN-γ and Th Lymphocyte Responses: Evaluation of Multiepitope Polypeptides as a Mode for Vaccine Delivery
Authors: Alexander Jeff , Oseroff Carla , Dahlberg Carol , Qin Mingsheng , Ishioka Glenn , Beebe Melanie , Fikes John , Newman Mark , Chesnut Robert W. , Morton Phillip A. , Fok Kam , Appella Ettore , Sette Alessandro
Published: April 2014

Proteins are generally regarded as ineffective immunogens for CTL responses. We synthesized a 100-mer decaepitope polypeptide and tested its capacity to induce multiple CD8+ IFN-γ and Th lymphocyte (HTL) responses in HLA transgenic mice. Following a single immunization in the absence of adjuvant, significant IFN-γ in vitro recall responses were detected for all epitopes included in the construct (six A2.1-, three A11-restricted CTL epitopes, and one universal HTL epitope). Immunization with truncated forms of the decaepitope polypeptide was used to demonstrate that optimal immunogenicity was associated with a size of at least 30–40 residues (3–4 epitopes). Solubility analyses of the truncated constructs were used to identify a correlation between immunogenicity for IFN-γ responses and the propensity of these constructs to form particulate aggregates. Although the decaepitope polypeptide and a pool of epitopes emulsified in IFA elicited similar levels of CD8+ responses using fresh splenocytes, we found that the decaepitope polypeptide more effectively primed for in vitro recall CD8+ T cell responses. Finally, immunogenicity comparisons were also made between the decaepitope polypeptide and a corresponding gene encoding the same polypeptide delivered by naked DNA immunization. Although naked DNA immunization induced somewhat greater direct ex vivo and in vitro recall responses 2 wk after a single immunization, only the polypeptide induced significant in vitro recall responses 6 wk following the priming immunization. These studies support further evaluation of multiepitope polypeptide vaccines for induction of CD8+ IFN-γ and HTL responses.
A Novel Role for IL-3: Human Monocytes Cultured in the Presence of IL-3 and IL-4 Differentiate into Dendritic Cells That Produce Less IL-12 and Shift Th Cell Responses Toward a Th2 Cytokine Pattern
Authors: Ebner Susanne , Hofer Susanne , Nguyen Van Anh , Fürhapter Christina , Herold Manfred , Fritsch Peter , Heufler Christine , Romani Nikolaus
Published: April 2014

Dendritic cells (DC) derived from plasmacytoid precursors depend on IL-3 for survival and proliferation in culture, and they induce preferentially Th2 responses. Monocytes express not only GM-CSF receptors, but also IL-3Rs. Therefore, we examined whether IL-3 had an effect on the functional plasticity of human monocyte-derived DC generated in a cell culture system that is widely used in immunotherapy. DC were generated with IL-3 (instead of GM-CSF) and IL-4. Yields, maturation, phenotype (surface markers and Toll-like receptors), morphology, and immunostimulatory capacity were similar. Only CD1a was differentially expressed, being absent on IL-3-treated DC. In response to CD40 ligation DC generated in the presence of IL-3 secreted significantly less IL-12 p70 and more IL-10 compared with DC grown with GM-CSF. Coculture of naive allogeneic CD4+ T cells with DC generated in the presence of IL-3 induced T cells to produce significantly more IL-5 and IL-4 and less IFN-γ compared with stimulation with DC generated with GM-CSF. These data extend the evidence that different cytokine environments during differentiation of monocyte-derived DC can modify their Th cell-inducing properties. A hitherto unrecognized effect of IL-3 on DC was defined, namely suppression of IL-12 secretion and a resulting shift from Th1 toward Th2.
KIR2DL4 (CD158d), an NK Cell-Activating Receptor with Inhibitory Potential
Authors: Faure Mathias , Long Eric O.
Published: April 2014

KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating function of KIR2DL4, and whether it can provide inhibitory signals, is not known. Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane region that is required for the activation signal. The activity of the mutated KIR2DL4 molecules was tested in a redirected lysis assay. The ITIM was not necessary for activation of lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4 inhibited the signal delivered by the activating receptor CD16. In pull-down experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory potential in addition to its activating function.