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Adaptation of Three Different Apoptotic Methods in Equine Bronchoalveolar Cells and Comparison of Bronchoalveolar Lavage Cell Apoptosis in Normal and COPD Affected Horses Before and After Dexamethasone AdministrationLeichner, Teri Lynn 25 July 2001 (has links)
Recent studies suggest that lymphocyte apoptosis serves to regulate pulmonary inflammation. Equine COPD, an allergic disease of the lower airway, is likely due to dysregulation of the pulmonary immune response. In this study, the hypothesis tested was COPD affected horses would have less apoptotic airway lymphocytes than control horses during clinical disease. To achieve this, 3 methods of measuring apoptosis, Vindelov's propidium iodide with Triton-X (PI/Triton-X), 7-aminoactinomycin D (7-AAD), and Annexin V with propidium iodide (Annexin/PI) were evaluated in equine airway lymphocytes. A significant linear relationship was found for equine bronchoalveolar lavage (BAL) lymphocytes stained with 7-AAD and Annexin/PI . No relationship was identified with cells stained with PI/Triton-X and Annexin/PI, and 7-AAD and PI/Triton-X indicating that methods which preserve cell membrane characteristics are more comparable when measuring BAL lymphocytes apoptosis in a heterogeneous population of cells. Additionally, all stains appear to perform the same in COPD and normal horses in remission and disease.
Comparison of predominately BAL lymphocyte apoptosis using the above methods were performed at baseline, after natural challenge, and after dexamethasone administration in nine horses, five of which were affected with COPD. No differences in bronchoalveolar lavage lymphocyte apoptosis between COPD and control horses were detected either before or after dexamethasone administration, although numerical trends in COPD horses identified less apoptosis after natural challenge indicating that defective apoptosis may play a role in equine COPD pathogenesis. Dexamethasone administration was associated with trends of improvement in the pulmonary gas exchange and increased apoptosis toward baseline in the COPD horses. / Master of Science
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Modélisation du risque de crédit de contrepartie / Modeling conterparty risk creditKettani, Othmane 19 October 2017 (has links)
On définit le risque de contrepartie comme le risque de détérioration de la qualité de crédit entrainant une incapacité de la contrepartie à remplir ses obligations contractuelles. De nos jours, ce risque ne se limite plus aux entreprises, mais s'est également étendu aux banques et autres institutions financières. Par conséquent, toute entité participant aux marchés dérivés OTC est exposée à ce risque. La «Credit Value Adjustment» (CVA) est la valeur de marché du risque de contrepartie. En raison de sa complexité, la mise en œuvre de la CVA demeure l'un des plus grands défis auxquels les banques font face depuis la dernière crise. Pour la plupart d’entre elles, sa mise en production nécessite des changements majeurs de l’infrastructure actuelle. En outre, le régulateur, dont le but est de renforcer la stabilité des marchés financiers, s’est également intéressé à la CVA en introduisant une nouvelle charge en capital liée au risque de contrepartie. Les contributions de notre thèse à la littérature existante sur le sujet se trouvent essentiellement aux chapitres 2, 3 et 4 du manuscrit. Dans les chapitres 2 et 3, nous proposons deux méthodes innovatrices pour le calcul de la CVA. Le chapitre 4 est, quant à lui, entièrement dédié à l’étude de la charge en capital réglementaire sous la régulation FRTB-CVA. / Counterparty risk is defined as the risk of credit worthiness deterioration, making the counterparty unable to meet its contractual obligations. Nowadays, this risk is no longer confined to corporate clients but has spread out to other banks and financial institutions. As a consequence, any firm participating in the over-the-counter (OTC) derivatives market is exposed to this risk. Credit Value Adjustment (CVA) is the market value of counterparty credit risk. Implementation of CVA still remains one of the biggest challenges banks face since the last financial crisis, due to its complexity and cost of implementation. For most banks, pricing the whole CVA book requires major changes on the infrastructure they currently have. Furthermore, regulatory responses to the last financial turmoil aimed at strengthening the financial system by introducing new capital requirements. The Basel III regulatory standard was developed in this respect, prescribing an additional capital charge to cover CVA losses.Our contributions to the relevant literature are chapters 2, 3 and 4. In chapters 2 and 3, we propose two innovative approaches to compute CVA that allow a huge reduction in computational costs. Chapter 4 is devoted to the study of the CVA capital charge under the new FRTB-CVA regulation.
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Conception et validation d'une assistance numérique domiciliaire pour la personne âgée en perte d'autonomie / Conception and validation of an assisted living platform for the older adult with finctional declineDupuy, Lucile 30 November 2016 (has links)
Avec le vieillissement de la population, le maintien à domicile des personnes âgées est devenu un enjeu majeur pour les pays développés et émergents. Parmi les solutions clés à explorer, les gérontechnologies sont considérées comme des plus prometteuses sans toutefois avoir apporté la preuve de leur efficacité pour l’autonomie domiciliaire, voire même être utilisables et acceptables pour le public visé. Dans ce contexte, une méthodologie de conception centrée-utilisateur a été mise en place pour proposer une plateforme d’assistance domiciliaire multi-tâches et multi-domaines (soutenant à la fois les activités quotidiennes, la sécurité de la personne et de son domicile et le lien social) ciblant un public âgé fragile en perte d’autonomie. Cette plateforme est appelée DomAssist. Sur la base d’une analyse des capacités physiques, cognitives et fonctionnelles en présence (étude 1) et des besoins d’assistance (étude 2) de notre échantillon d’étude, DomAssist a été conçu avec pour originalité une offre de services multi-domaines. En effet, la plateforme s’appuie d’une part sur un système de surveillance d’activités pour délivrer des assistances dites « context-aware » (étude 3) et d’autre part sur un système d’interaction homme-machine unifié et simplifié (étude 4), et ceci tout en promouvant l’auto-détermination (étude 5). Les résultats ont étayé la fiabilité du système de surveillance d’activités, et renforcé le bien-fondé de nos principes de conception concernant le système unifié d’interaction; et le soutien de l’auto-détermination. Notamment un rendu positif concernant l’utilisabilité et l’acceptabilité du système, et un effet bénéfique sur le sentiment de l’autodétermination des utilisateurs âgés ont été obtenus. De là, une dernière étude (étude 6) a évalué les bénéfices apportés après 6 mois d’utilisation de la plateforme, en termes de capacités fonctionnelles des participants fragiles, et de réduction du fardeau de l’aidant. Un effet positif (effet « protecteur » observé par les aidants professionnels) de DomAssist sur le statut fonctionnel des participants équipés (comparé aux contrôles) a été observé ainsi qu’une réduction du fardeau objectif de leur aidant. Au total, les résultats de ce travail pilote sont encourageants et ouvrent de nombreuses perspectives de recherche à fort potentiel d’impact sociétal concernant la problématique du maintien à domicile des personnes âgées / With the increase of life expectancy, aging in place is today a major concern for developed and emerging countries. Among the key solutions to explore, gerontechnologies are seen as the most promising. However, their evidence-based efficacy remains to be demonstrated for independent living or even for their usability and acceptance by the targeted old users. In this context, a user-centered conception methodology has been implemented for designing a multi-task and multi-domain (supporting everyday activities, safety, and social participation) assisted living platform targeting frail older adults with functional decline. This platform is named HomeAssist. Based on an analysis of physical, cognitive and fonctional abilities (study 1) and assistive technology needs (study 2) of our sample, HomeAssist has been designed with the originality of providing multi-domain services. Indeed, HomeAssist proposes an activity monitoring system to provide context-aware assistance (study 3), and a unified human-computer interaction system (study 4); while promoting self-determination (study 5). Results underpined the reliability of our activity monitoring system, and reinforced the rationale of our design principles, concerning the unified interaction system and the self-determination support. Notably, positive outcomes in terms of usability and acceptance of the system, as well as benefits concerning users’ feeling of self-determination have been obtained. From this, a last study (study 6) evaluated the benefits from a six-month use of HomeAssist, on functional abilities of frail older adults and caregiver burden. A positive effect of HomeAssist on functional status was obtained (“protective” effect reported by the professional caregivers), as well as a reduction of objective dimension of caregiver burden. Taken together, the results from these pilot studies are encouraging and open numerous research perspectives with high societal impact concerning the promotion of aging in place.
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CT Findings of Pulmonary HypertensionPatel, Akash 25 May 2017 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Primary pulmonary hypertension (PPH) has an extremely poor prognosis with a mean survival time of 2‐3 years from time of diagnosis. Hemodynamically, PPH is defined with a mPAP of ≥ 25 mm Hg. Currently, RHC is the gold standard for measuring the arterial pressures and diagnosing PPH; however, it is an incredibly invasive procedure. Our study will show whether CT angiography can be considered as a non‐invasive alternative for diagnosing PPH. Studies in the past have shown CT measurements of the MPAD and MPAD/AAD ratio having strong correlations with PPH. In addition to those measurements, we want to show if other CT parameters also have a correlation with PPH. Some of these novel measurements include the interventricular septal deviation and the Elizabeth Taylor sign. The interventricular septum is normally bowing to the right in a non‐pathological state. If it is straight or bowing to the left, this will indicate increased right ventricular pressures which would be indicative of PPH. Straight will indicate increased RV pressures, and bowing to the left will be considered markedly increased RV pressures. The Elizabeth Taylor sign is the ratio of the diameter of the segmental bronchi and its corresponding artery. We will hypothesize that the artery will be much larger than the bronchi in patients with PPH. Other measurements will include the left and right pulmonary arteries. This study is a retrospective review of subjects who underwent an otherwise unremarkable CT pulmonary artery angiogram. Subjects with pulmonary embolism or other acute pulmonary diseases are excluded. For each subject, the following CT findings are obtained: main pulmonary artery diameter (mPAD), ratio of mPAD to ascending aorta, right and left pulmonary artery diameters, ratio of segmental pulmonary artery to corresponding bronchus, and interventricular septal displacement. Straightening of the interventricular septum qualifies as increased right ventricular septal pressure and right‐to‐left bowing of the septum qualifies as a marked increase. Mean pulmonary artery pressure measured on any prior/subsequent RHC or echocardiogram within 3 months of the CT is recorded. Any past medical history of connective tissue disease is noted. Descriptive data are calculated and correlations are done to assess for presence and strength of associations among variables. Data from 484 subjects are collected. Incidence rate of pulmonary hypertension isv13% (n=63). 52% (n=33) of the subjects with pulmonary hypertension are female with an average age of 55 years. mPA diameter (p<0.001), mPA:AA ratio (p<0.001), right (p<0.001) and left pulmonary artery (p=0.004) diameters are predictors of pulmonary hypertension. sPA:B ratio (p=0.08) and interventricular septal displacement (p=0.96) are not predictive of pulmonary hypertension. This study supports an association of mPA diameter, mPA:AA ratio, right and left pulmonary artery diameters with pulmonary hypertension diagnosed by RHC or echocardiogram. Prospective research is warranted to confirm and establish threshold values for each variable. Currently, an invasive RHC remains the most accurate method of diagnosis. Correlating CT findings with pulmonary hypertension would allow clinicians to use CT as a noninvasive screening tool.
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Exploring Branded Flash Mobs : A study of the impact of branded flash mobs on consumer behavior and consumer experienceGrant, Philip January 2014 (has links)
The desire of every marketer is to develop and maintain strong customer relationships. One way this can be accomplished is through effective advertising. Marketers have recently begun to brand flash mobs as a way to effectuate strong brand relationships. Even so, it is unclear whether or not the branding of flash mobs supports or frustrates this pursuit. Therefore, the goal of this thesis is to help marketers understand the potential impact that branded flash mobs may have on consumer behaviour and brand relationships. Since these interactions are complex we need to observe the convoluted whole from untangled vantage points. Marketing scholars and researchers must then attempt to understand the latent opportunities and unsuspecting dangers when branding a flash mob. Toward answering this end, four distinct research studies were used to examine the phenomenon from four different perspectives. The aim of the first paper is twofold. First, it deductively seeks to understand how to categorize branded flash mobs within the marketing literature through an historical and cultural analysis of the phenomenon. Exploratory in nature, this study then employs a mixed methods approach to understand how marketers are currently using flash mobs, and more importantly, if branded flash mobs are an effective tool of communication and persuasion. In the second paper, a field experiment was conducted to assess the impact of a branded flash mob on consumers’ emotions, consumer experience and connectedness in a public market. Qualitative interviews were used to capture the data. Shifting perspectives, the third paper seeks to understand why some branded flash mobs fail to ‘go viral’. Using of a number of focus groups, participants were asked to watch several branded flash mob videos and discuss their willingness to share them online (e.g., email, Facebook, or Twitter). Toward a better understanding of the impact of branded flash mobs on brand equity, the final paper evaluates viewers’ attitude toward the ad. Using netnographic techniques (Kozinets, 2002) 2,882 YouTube comments from three virally successful branded flash mobs ads were examined to understand how branded flash mobs affect brand equity. Responses grouped into one of four archetypical attitudes, each of which has a distinct impact on brand equity. Motivated by the potential for widespread exposure at a relatively low cost, marketers continue to produce branded flash mobs. Sometimes they are fresh and creative, while at others they are out of tune with the spirit of the phenomenon. This thesis uncovers the impact of these efforts on consumer behaviour and brand equity, and concludes with a guide for managers to consider when planning their next branded flash mob. An acknowledgement of the limitations and an outline for directions of future research are also presented. / <p>QC 20140521</p>
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A Deep Learning Approach to Brain Tracking of SoundHermansson, Oscar January 2022 (has links)
Objectives: Development of accurate auditory attention decoding (AAD) algorithms, capable of identifying the attended sound source from the speech evoked electroencephalography (EEG) responses, could lead to new solutions for hearing impaired listeners: neuro-steered hearing aids. Many of the existing AAD algorithms are either inaccurate or very slow. Therefore, there is a need to develop new EEG-based AAD methods. The first objective of this project was to investigate deep neural network (DNN) models for AAD and compare them to the state-of-the-art linear models. The second objective was to investigate whether generative adversarial networks (GANs) could be used for speech-evoked EEGdata augmentation to improve the AAD performance. Design: The proposed methods were tested in a dataset of 34 participants who performed an auditory attention task. They were instructed to attend to one of the two talkers in the front and ignore the talker on the other side and back-ground noise behind them, while high density EEG was recorded. Main Results: The linear models had an average attended vs ignored speech classification accuracy of 95.87% and 50% for ∼30 second and 8 seconds long time windows, respectively. A DNN model designed for AAD resulted in an average classification accuracy of 82.32% and 58.03% for ∼30 second and 8 seconds long time windows, respectively, when trained only on the real EEG data. The results show that GANs generated relatively realistic speech-evoked EEG signals. A DNN trained with GAN-generated data resulted in an average accuracy 90.25% for 8 seconds long time windows. On shorter trials the GAN-generated EEG data have shown to significantly improve classification performances, when compared to models only trained on real EEG data. Conclusion: The results suggest that DNN models can outperform linear models in AAD tasks, and that GAN-based EEG data augmentation can be used to further improve DNN performance. These results extend prior work and brings us closer to the use of EEG for decoding auditory attention in next-generation neuro-steered hearing aids.
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Influence de la présence d’un personnage, d’un visage et de la direction du regard en communication publicitaire / Influence of character and face presence, and gaze direction in advertising communicationAdil, Safaa 17 December 2015 (has links)
Cette recherche a pour objectif d’examiner l’influence de la présence, dans des annonces presse, d’un personnage, d’un visage ou de la direction d’un regard sur l’attention portée à cette annonce ainsi que sur la mémorisation et les évaluations de cette annonce. Afin d’éprouver nos hypothèses quatre expérimentations ont été menées. Dans l’une d’entre elles un système eye-tracking a été utilisé permettant de mieux cerner les processus attentionnels. Pour nous rapprocher des conditions d’exposition habituelles à la publicité, les annonces presse ont été dissimulées dans un magazine fictif. Les résultats obtenus montrent que la présence du personnage ou du visage (versus leur absence), ainsi que le regard dirigé vers le produit (versus le regard dirigé vers l’observateur), exercent une influence sur l’attention portée à l’annonce, la mémorisation de son contenu et son évaluation. / This research aims to examine the influence of the presence in a print advertisement of a character, a face or a gaze direction (gaze directed toward the product versus gaze directed toward the observer) on attention toward the advertisement, the memorization and the evaluation of the advertisement content. To test our hypotheses, four experiments were conducted. In one of these experiments an eye-tracker has been used to better measure attentional processes. In order to approach the ordinary conditions of exposure to advertising, print advertisements were inserted in a fictive magazine (folder test procedure). The results show that the presence of the character or the face (versus their absence) and the gaze directed toward the product (versus gaze directed toward the observer) improve the attention toward the advertisement, the memorization and the assessment of advertisement content.
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Is Political Activism the New Black? : Consumers' Attitudes toward a Brand that uses Political Activism in AdvertisementKarlsson, Cornelia, Kljako, Azra, Pauldén, Therése January 2017 (has links)
Background: In 2017, brands have started to use their advertisements to take stance in political issues. However, since this trend has emerged in 2017, research in the field is limited. The research that is available is focused on how attitudes toward advertisements in general affect consumer attitudes toward the brand, which calls for deeper knowledge on how the political activism trend affect consumers’ attitudes. Purpose: To explore how political activism in advertisements affect consumers’ attitudes toward the brand behind the advertisement. Research Question: How does political activism in advertisements affect consumers’ attitudes toward the brand? Methodology: This study is of qualitative nature and took an explorative approach. Data was collected through semi-structured interviews based on a convenience sample of 11 respondents. Conclusion: The main findings from this study was that political activism in advertisement had an enhancing affect on respondents’ attitudes toward the brand behind the advertisement. Respondents that had positive attitudes toward the brand before were more positive toward the brand after the political advertisement, while the ones who were negative became more negative after the political advertisement. Keywords Political activism, attitudes toward advertisements (Aad), attitudes toward brands (Ab), incongruity and involvement.
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The General Abilities Index as a Third Method of Diagnosing Specific Learning DisabilitiesSims-Cutler, Kristin M. 01 January 2014 (has links)
Many studies have investigated problems with the ability achievement discrepancy (AAD) method of diagnosing specific learning disabilities (SLDs). The definition of an SLD includes the presence of a deficit in one or more cognitive processing systems. Researchers in other studies found that the AAD method overdiagnoses English language learners and students from low socioeconomic backgrounds, and underdiagnoses students with cognitive processing deficits. Although SLD diagnostic methods have been widely researched, much less information is available regarding SLD diagnostic methods that predict important student outcomes, such as high school completion. The General Abilities Index (GAI) is an SLD diagnostic method that can identify cognitive processing deficits. This study examined the relationships between cognitive processing deficits and the GAI method, high school completion status, performance on state standards assessments, and SLD eligibility. Using a multivariate, nonexperimental design, this study analyzed 149 datasets from records of students tested for an SLD between 1996 to 2013. A GLM analysis found that several types of cognitive processing deficits predicted math and writing performance on the state standards assessment and predicted not being diagnosed with an SLD, while the GAI method failed to predict any relationship with the dependent variables. Positive social changes from this study may include improved SLD diagnostic practices and improved educational interventions that target the cognitive processing deficits. Improved educational outcomes for SLD persons may reduce the high rates of unemployment, substance abuse, and incarceration experienced by the adult SLD population.
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The Role of Eosinophils in the Regulation of CD4+ T helper 2 Regulated InflammationMacKenzie, Jason Roderick, Jason.Mackenzie@ipaustralia.gov.au January 2004 (has links)
The eosinophil is a leukocyte whose intracellular mediators are considered to play a
central role in the pathogenesis of allergic diseases, including allergic asthma, allergic
rhinitis and atopic dermatitis, and which is also involved in immunological responses to
parasites. Eosinophil differentiation and maturation from bone marrow progenitors is
regulated by interleukin-5 (IL-5), which may be secreted by T helper 2 (Th2) T
lymphocytes, and is consistently upregulated in allergic conditions. Eotaxin is a potent
chemoattractant for circulating and tissue eosinophils, and the production of this
chemokine promotes eosinophil infiltration and accumulation within sites of allergic
inflammation.¶
Eosinophils obtained from inflammatory tissues and secretions display an altered
phenotype in comparison to peripheral blood eosinophils, with increased surface
expression of major histocompatibility complex (MHC) proteins and adhesion
molecules (Hansel et al., 1991), and migration across the microvascular endothelium
may also increase their capacity to generate an oxidative burst (Walker et al., 1993;
Yamamoto et al., 2000). Eosinophils are phagocytic cells, and have been shown to
present simple (no requirement for intracellular processing) and complex antigens to
MHC-restricted, antigen-specific T lymphocytes (Del Pozo et al., 1992; Weller et al.,
1993). Furthermore, eosinophils express the costimulatory molecules required for
effective antigen presentation (Tamura et al., 1996), and ligation of costimulatory
molecules on the eosinophil cell surface can induce the release of eosinophil derived
cytokines (Woerly et al., 1999; Woerly et al., 2002). Therefore the eosinophil may also
regulate immune responses.¶
To date, no studies have demonstrated the ability of eosinophils to modulate activated T
lymphocyte function via presentation of relevant antigen in the context of MHC class II
(MHC-II), concomitant with Th2 cytokine release. In the experiments described in this
thesis, murine eosinophils have been observed to rapidly migrate to sites of antigen
deposition within the airways mucosa of naïve mice, suggesting a potential role for this
granulocyte in the primary response to inhaled antigen. However, human allergic
diseases are often diagnosed after the establishment of allergic responses, and symptom
development. Therefore, a murine model of allergic airways disease (AAD) was used to
investigate the ability for eosinophils to participate as antigen presenting cells (APCs),
and thereby modulate activated T lymphocyte function both in vitro and in vivo.
Detailed histological analysis of the pulmonary draining lymph nodes following antigen
challenge in sensitised mice revealed a rapid infiltration of eosinophils into this tissue,
which preceded the accumulation of eosinophils in bronchoalveolar lavage fluid
(BALF). This suggested that eosinophils were preferentially translocating to the
draining lymph nodes following antigen challenge, and that the subsequent
accumulation of these cells in the BALF was a consequence of continued antigen
delivery to the lower airways.¶
Eosinophil trafficking to lymphoid tissue via the afferent lymphatics was substantiated
using electron microscopy of lymph node sections and the intravenous (i.v.) transfer of
fluorescently labeled eosinophils, which did not traffic to lymph nodes via the blood.
During the resolution of AAD, eosinophils were noted for their persistence in the
pulmonary draining lymph nodes. These observations suggested a continued modulation
of T cell function by lymph node dwelling eosinophils during AAD resolution,
particularly in light of recent observations for draining lymph node T cell proliferation
following instillation of antigen-pulsed eosinophils into the allergic mouse lung (Shi et
al., 2000).¶
To further investigate the antigen presenting capacity, eosinophils were obtained from
the BALF of mice with AAD, and their surface expression of MHC class II (MHC-II)
proteins and costimulatory molecules confirmed using flow cytometric analysis. The
ability to acquire and process complex antigen both in vitro and in vivo was also
confirmed using naturally quenching fluorescenated ovalbumin (OVA), which is
degraded into fluorescent peptides by the action of intracellular proteases. Thus,
eosinophil expression of the surface molecules necessary for effective antigen
presentation was confirmed, as was their ability to process complex antigen. Further
investigations revealed that eosinophils can present complex OVA antigen to CD4+ T
lymphocytes obtained from the allergic mouse, and to in vitro derived OVA-specific
Th2 cells. In the presence of exogenous antigen, eosinophils co-cultured with T
lymphocytes were able to induce Th2 cytokine production, and demonstrated an ability
for eosinophils to modulate T lymphocyte function in vitro.¶
The ability for eosinophils to act as antigen presenting cells in vivo was also
investigated. Eosinophils obtained from the antigen-saturated lungs of OVA sensitised
and challenged mice were transferred to the peritoneal cavities of naïve host mice.
When subsequently challenged with aerosolised OVA, eosinophil recipients developed
a pulmonary eosinophilia similar to that of OVA sensitised and challenged mice. To
validate this finding, the experimental procedure was altered to accommodate the use of
non-allergy derived eosinophils, which were pulsed with OVA in vitro, prior to transfer
into naïve recipients. When subsequently challenged with aerosolised OVA, eosinophil
recipients developed a peripheral blood and pulmonary eosinophilia, and stimulation
with OVA induced IL-5 and IL-13 cytokine production from pulmonary draining lymph
node cells. Notably, the AAD induced by transfer of antigen pulsed eosinophils did not
induce detectable OVA-specific IgG1, which may be attributed to the lack of soluble
antigen required for B cell antibody production.¶
During the course of these investigations, an OVA T cell receptor (TCR) transgenic
mouse (OT-II) was procured with a view to defining the interaction between eosinophils
and activated T lymphocytes (Barnden et al., 1998). Despite having specificity for the
OVA323-339 peptide, an immunodominant epitope that skews naïve T cell responses
towards Th2 cytokine release (Janssen et al., 2000), T lymphocytes from the OT-II
mouse preferentially secreted IFN-γ in response to stimulation with either OVA peptide
or OVA. These mice were further characterised in a mouse model of AAD, and found to
be refractory to disease induction and progression, which may be attributed to
significant IFN-γ secretion by transgenic CD4+ T lymphocytes during antigen
sensitisation. Indeed, these cells were noted for their ability to attenuate pulmonary
eosinophilia when transferred to OVA sensitised and challenged wild type mice,
although serum OVA-specific IgG1, peripheral blood eosinophilia levels and airways
response to methacholine challenge remained intact.¶
Knowledge of the biased Th1 phenotype in naïve OT-II provided a unique opportunity
to investigate the fate of T lymphocytes bearing high affinity OVA-specific TCRs
following neonatal antigen exposure to soluble OVA. In a previous study, subcutaneous
(s.c.) administration of soluble OVA to wild type neonatal mice was suspected to have
deleted OVA-specific T cells from the T cell repertoire (Hogan et al., 1998a). Using
flow cytometry and TCR specific antibody, the delivery of s.c. OVA to OT-II neonates did not alter transgenic T cell populations in adult mice. Instead, it was surprising to
find a skewing towards the Th2 phenotype and loss of IFN-γ secretion following OVA
sensitisation and challenge in adult mice. A mechanism for this reprogramming of the
transgenic T cell from the Th1 to a Th2 phenotype following OT-II neonatal exposure
to soluble OVA is proposed, and further experimentation may validate this hypothesis.¶
In conclusion, eosinophils residing in the allergic lung have the capacity to interact with
activated T cells, both within this tissue and the draining lymph nodes. Despite their
relative inefficiency as antigen presenting cells (Mawhorter et al., 1994), eosinophils
may participate en masse in the serial triggering of activated TCRs, and provide
appropriate costimulatory signals that modulate T lymphocyte function. Through the
elaboration of Th2 cytokines and stimulation of T cell proliferation, antigen presenting
eosinophils may transiently prolong or exacerbate the symptoms of allergic diseases.
Alternatively, eosinophils presenting relevant antigens may inhibit T cell activity via
degranulation, and such activity has recently been observed in a parasite model (Shinkai
et al., 2002). Finally, experiments in the OT-II mouse have provided valuable
information to suggest that therapies designed to modulate eosinophil numbers in
allergic tissues through the secretion of opposing cytokines such as IFN-γ, may be of
limited benefit. The results shown here suggest that airways dysfunction remains intact
despite significantly reduced pulmonary eosinophilia
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