Immunodépression acquise en réanimation : approche expérimentale et cliniques des altérations lymphocytaires induites lors des syndromes septiques

Sepsis remains a major public healthcare issue. During sepsis, an important immunodepression develops, affecting particularly the T lymphocytes, major players of the immune response. Following a massive apoptosis, T lymphocytes display important functional and phenotypical alterations, which are associated with higher risk of secondary infections and higher mortality. Mechanisms involved in the induction of such alterations are not fully understood. The aim of this study was to analyze those mechanisms through the development of ex vivo models. We optimized a test to measure T lymphocytes proliferative response, which can be used for the diagnosis of primary immunodeficiencies, as well as to clinically and experimentally study sepsis induced T lymphocytes alterations (SILA). First, we set up a model consisting in an incubation of PBMC (peripheral blood mononuclear cells) with LPS followed by specific T lymphocytes stimulation via its TCR. This model recapitulates indirect mechanisms likely to participate in SILA induction, mediated by monocytes. Then, we set up a model consisting in PBMC incubation with IL-10 followed by T lymphocytes stimulation with anti-CD2/3/28 antibody coated beads. This model may recapitulate direct and indirect mechanisms involved in SILA induction. Our results allowed us to improve the understanding of the mechanisms involved in SILA induction and to highlight its complexity. The ex-vivo models that we developed could be used for the evaluation of new therapeutic strategiesLes syndromes septiques restent à ce jour un problème majeur de santé publique. Une importante immunodépression est observée lors des syndromes septiques, affectant notamment les lymphocytes T, acteurs majeurs de la réponse immunitaire. En effet, après avoir subi une apoptose massive ils présentent d'importantes altérations fonctionnelles et phénotypiques, associées à un mauvais pronostic. Cependant les mécanismes impliqués dans le développement de ces altérations lymphocytaires induites par le sepsis (ALIS) sont encore mal connus. Le but de ce travail était d'étudier ces mécanismes à travers la mise au point de modèles ex-vivo. Nous avons optimisé un test de mesure de la réponse proliférative des lymphocytes T, utilisable pour le diagnostic des immunodéficiences primaires, comme pour l'étude expérimentale et clinique des ALIS. Nous avons développé un premier modèle ex vivo, reposant sur l'incubation de cellules mononuclées du sang périphérique (PBMC) en présence de LPS, suivie d'une stimulation spécifique des lymphocytes T via leur TCR. Ce modèle récapitule des mécanismes indirects potentiellement impliqués dans l'induction des ALIS, impliquant les monocytes. Puis, nous avons mis au point un modèle qui repose sur l'incubation de PBMC en présence d.IL-10, suivie d'une stimulation des lymphocytes T par des anticorps anti-CD2/CD3/CD28. Ce modèle pourrait reproduire des mécanismes directs et indirects impliqués dans l'induction des ALIS. Nos résultats nous ont permis d'améliorer la compréhension des mécanismes en jeux dans les ALIS et d'en souligner la complexité. Les modèles ex-vivo présentés pourraient permettre d'évaluer de nouvelles stratégies thérapeutique

FICHES DE THÈSES

International audienc

Clinical and experimental study of sepsis-induced T lymphocytes alterations in ICU patients

Les syndromes septiques restent à ce jour un problème majeur de santé publique. Une importante immunodépression est observée lors des syndromes septiques, affectant notamment les lymphocytes T, acteurs majeurs de la réponse immunitaire. En effet, après avoir subi une apoptose massive ils présentent d'importantes altérations fonctionnelles et phénotypiques, associées à un mauvais pronostic. Cependant les mécanismes impliqués dans le développement de ces altérations lymphocytaires induites par le sepsis (ALIS) sont encore mal connus. Le but de ce travail était d'étudier ces mécanismes à travers la mise au point de modèles ex-vivo. Nous avons optimisé un test de mesure de la réponse proliférative des lymphocytes T, utilisable pour le diagnostic des immunodéficiences primaires, comme pour l'étude expérimentale et clinique des ALIS. Nous avons développé un premier modèle ex vivo, reposant sur l'incubation de cellules mononuclées du sang périphérique (PBMC) en présence de LPS, suivie d'une stimulation spécifique des lymphocytes T via leur TCR. Ce modèle récapitule des mécanismes indirects potentiellement impliqués dans l'induction des ALIS, impliquant les monocytes. Puis, nous avons mis au point un modèle qui repose sur l'incubation de PBMC en présence d.IL-10, suivie d'une stimulation des lymphocytes T par des anticorps anti-CD2/CD3/CD28. Ce modèle pourrait reproduire des mécanismes directs et indirects impliqués dans l'induction des ALIS. Nos résultats nous ont permis d'améliorer la compréhension des mécanismes en jeux dans les ALIS et d'en souligner la complexité. Les modèles ex-vivo présentés pourraient permettre d'évaluer de nouvelles stratégies thérapeutiquesSepsis remains a major public healthcare issue. During sepsis, an important immunodepression develops, affecting particularly the T lymphocytes, major players of the immune response. Following a massive apoptosis, T lymphocytes display important functional and phenotypical alterations, which are associated with higher risk of secondary infections and higher mortality. Mechanisms involved in the induction of such alterations are not fully understood. The aim of this study was to analyze those mechanisms through the development of ex vivo models. We optimized a test to measure T lymphocytes proliferative response, which can be used for the diagnosis of primary immunodeficiencies, as well as to clinically and experimentally study sepsis induced T lymphocytes alterations (SILA). First, we set up a model consisting in an incubation of PBMC (peripheral blood mononuclear cells) with LPS followed by specific T lymphocytes stimulation via its TCR. This model recapitulates indirect mechanisms likely to participate in SILA induction, mediated by monocytes. Then, we set up a model consisting in PBMC incubation with IL-10 followed by T lymphocytes stimulation with anti-CD2/3/28 antibody coated beads. This model may recapitulate direct and indirect mechanisms involved in SILA induction. Our results allowed us to improve the understanding of the mechanisms involved in SILA induction and to highlight its complexity. The ex-vivo models that we developed could be used for the evaluation of new therapeutic strategie

Management of sales advisers and service climate: an experiment

International audiencePurpose: Although experts agree on the importance of service quality, sales force management practices are often far from conforming to their recommendations. The current use of sales contests with quantitative objectives on turnover or profit margin is evidence of this divergence. Sharma notes the need for a better understanding of the impact of such incentives on quality of service. In response to this call, the concept of "service climate" as an internal indicator of customer perception of service quality is studied. More specifically, the purpose of this paper is to consider which type of sales contest best preserves service climate.Design/methodology/approach: Four characteristics of sales contests are examined through an experimental approach. Salespeople's perception of service climate are measured. Hypotheses are tested with ANOVA.Findings: The study shows that sales contest can have a negative impact on the service climate. The results give indications as to which incentives are optimal in terms of service climate. Surprisingly, selective contests, with a ranked competition and few winners, would affect service climate to a lesser extent.Practical implications: The findings of this study are unexpected and indicate that sales managers need to pay attention not only to sales contest's characteristics but also their interaction. The sales contest is not an addition to but a combination of modalities.Originality/value: This study has both managerial and research implications for design and implementation of sales contest

Employer Branding Among Salespeople: An Exploratory Analysis of Glassdoor Reviews

International audienc

Management de la marque employeur.

International audienc

Coopetition in sales and commercial coopetition: When the coopetition in the sales contest is a source of performance

International audienc

Coopetition in sales and commercial coopetition: When the coopetition in the sales contest is a source of performance

International audienc

Temp workers: why be loyal?

International audienceThis paper addresses workers' loyalty toward a temp agency. Loyalty reduces contact and management costs, so temp agencies attempt to retain valuable workers. The study therefore focuses on factors that attach workers to their temp agency. This study offers an interdisciplinary approach, according to which the temporary worker is both an employee and a client of the agency. It highlights important factors that determine temp workers' loyalty to the agency, using a relational perspective. A hybrid model, based on social exchange theory, integrates services marketing and human resource management literature to explain the attachment of temporary workers to an agency. Social exchange theory offers an integrative framework for explaining a person's loyalty to an organisation (employer or supplier), based on reciprocity

De la congruence de valeurs à la marque employeur: quelles conséquences pour l'identification et le bouche‐à‐oreille vis‐à‐vis de l'organisation?

International audienceThe war for talent has led organizations to develop a strong employer brand to attract and retain skilled employees. Few studies have examined the antecedents and consequences of the internal employer brand. We focus on the influence of employee‐organization values congruence on the employee's perception of the employer brand and on the influence of the employer brand on organizational identification and positive word‐of‐mouth vis‐à‐vis the employer. Results from a survey of 308 employees show that the employer brand fully mediates the relationship between values congruence and organizational identification and positive word‐of‐mouth. These results have theoretical and managerial implications in terms of employer branding.La guerre des talents pousse les organisations à développer une marque employeur forte afin d'attirer et retenir les salariés compétents. Néanmoins, peu d'études portent sur les antécédents et les conséquences de la marque employeur interne. Cette recherche s'intéresse d'une part, à l'influence de la congruence des valeurs collaborateur‐entreprise sur les perceptions de la marque employeur et d'autre part, à l'influence de celle‐ci sur l'identification organisationnelle et le bouche‐à‐oreille positif vis‐à‐vis de l'employeur. Les résultats de l'enquête menée auprès de 308 salariés montrent que la marque employeur médiatise complètement la relation entre, d'une part, la congruence des valeurs et, d'autre part, l'identification organisationnelle et le bouche‐à‐oreille positif des collaborateurs. Ces résultats ont des implications théoriques et managériales concernant la gestion de la marque employeur