Tesis sobre el tema "Immunosuppression – Maladies"
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Viau, Muriel. "Effets des superantigènes B in vitro et in vivo dans un modèle de souris transgèniques humanisées". Paris 13, 2004. http://www.theses.fr/2004PA132031.
Texto completoChanson, Laura Bohne Wolf. "Impact des troubles anxio-dépressifs sur les tissus de la cavité buccale". [S.l.] : [s.n.], 2008. http://castore.univ-nantes.fr/castore/GetOAIRef?idDoc=52216.
Texto completoDumetz, Fabien. "Les antigènes de surface de Flavobacterium psychrophilum : approche protéomique et caractérisation de deux protéines (OmpA/P60 et OmpH/P18)". Bordeaux 2, 2006. http://www.theses.fr/2006BOR21363.
Texto completoFlavobacterium psychrophilum is a Gram negative bacteria responsible for fish infection. We used a proteomic approach to identify some outer membrane components such as putative adhesins, proteins involved in iron acquisition or in efflux systems, a HtrA homologue and some other molecules with unknown function. Several major antigens have been identified in the outer membrane including the two components OmpH/P18 and OmpA/P60. They are surface-exposed since they were completely digested by in situ proteinase K treatment and the two monospecific sera were bacteriostatic/bactericidal. Vaccination trials showed that both proteins can induce a high titter of specific antibodies which are protective. Collectively, these results indicate that these two proteins could be used in future vaccine development as promising candidate antigens
Lefevre, Camille. "Exploration fonctionnelle des cellules souches du tissu adipeux dans l'émergence des maladies de l'obésité". Electronic Thesis or Diss., Lyon, 2020. https://n2t.net/ark:/47881/m6319v9s.
Texto completoObesity induces a chronic inflammation responsible for complications (diabetes, cardiovascular diseases) where adipose tissue plays a central role. At the onset of obesity, inflammation is at low grade suggesting the control by immunosuppressive mechanisms that decrease with obesity, promoting complications. Adipose stem cells (ASC) support the development and the homeostasis of adipose tissue in subcutaneous and visceral adipose depots. Inflammatory stimuli induce immunosuppressive functions in ASC in vitro, but published data report that ASC isolated from inflammatory adipose tissues in established obesity have lost these properties. The role of ASC in the immune homeostasis of adipose tissue is poorly known. We made the hypothesis that immunosuppressive properties of ASC are induced since the onset of obesity and that their alterations contribute to complications. To address this question, I performed two protocols of diet induced obesity in mice and I explored the functions of ASC isolated from subcutaneous (S-ASC) and visceral (V-ASC) adipose depots. My results show major differences in the proliferation and the differentiation potential of ASC from distinct adipose depots, according to published data. We reveal that these differences correlate with distinct metabolomes, V-ASC having lower mitochondrial and higher glycolytic activity than S-ASC. Using this model, we studied the immunosuppressive functions of ASC in early obesity in both adipose depots. To this end we performed a kinetic of 6, 10 and 14 weeks of high fat diet (HF) in C57Bl/6 mice. This timing covered low grade inflammation progress from glucose intolerance with 6 weeks of diet in the absence of adipose tissue inflammation, to insulin resistance at 14 weeks of diet associated with visceral, but not subcutaneous, adipose tissue inflammation. My results show that at 6 weeks of HF diet, V-ASC attracted macrophages and inhibited the pro-inflammatory M1 polarization of these cells. At the same time, S-ASC completely suppressed the proliferation of activated T lymphocytes and strongly inhibited their migration. This study shows (i) that CSA from both adipose depots are activated by HF diet, independently of inflammation and diet time, (ii) that the induced immunosuppressive properties target distinct immune cells, (iii) that they are maintained with resistance to insulin. The analysis of adipose tissue composition showed that the ASC population decreased and had lower proliferation rate with HF diet. This indicate that at the onset of obesity, intrinsic properties of ASC were maintained in vitro but their environment altered their maintenance in both adipose depots. In a second protocol, I explored the consequences of maternal overnutrition during lactation on the properties of ASC in the adulthood. It has been reported that these conditions favorize the development of metabolic diseases in the offspring. We wondered whether ASC are targeted by maternal diet and develop long term alterations. I isolated S- and V-ASC from the offspring 6 weeks after weaning and I explored the influence of a HF post-weaning diet. RNA seq analysis showed that maternal diet altered the transcriptome of ASC in the adulthood and induced glucose intolerance, even in animal fed with a standard diet after weaning. Gene expression altered in ASC support cell death, metabolic stress, transcription, protein synthesis. Some genes are only affected by the mother’s diet. For genes associated with cell death, differential expressions induced by HF diet are increased when cumulated with mother’s HF diet. These results show that alterations of ASC precede the complications in the adult offspring. ASC can thus be programmed by maternal overnutrition and are the probable vectors of later adipose tissue dysfunctions
Paul, Carle. "Développement des inhibiteurs de la calcineurine pour le traitement des maladies inflammatoires cutanées : de l' immunosuppression systémique à l'immunomodulation topique". Paris 7, 2005. http://www.theses.fr/2005PA077076.
Texto completoYedikardachian, Christine. "Prévention et traitement de la varicelle chez l'enfant immunodéprimé". Paris 5, 1988. http://www.theses.fr/1988PA05P138.
Texto completoEscaffre, Olivier. "Bases moléculaires du pouvoir pathogène et développement d’une méthode de quantification différentielle des quatre brins génomiques chez l’Avibirnavirus de la bursite infectieuse". Rennes 1, 2011. http://www.theses.fr/2011REN1S005.
Texto completoInfectious Bursal Disease (IBD) is an infectious disease of young chickens (Gallus gallus) caused by a bisegmented (A & B) double-stranded RNA genome virus (IBDV, family Birnaviridae, genus Avibirnavirus). The virus replication cycle is not fully described regarding the time and place of strand synthesis. In a first part of this study, four real-time quantitative RT-PCR methods, able to quantify specifically each strand of the IBDV genome, were developed. Implementation of these methods on purified IBDV particles and on a kinetic study of in-vitro strand production provided interesting data as to the possible genomic content of virus particles and to the replication model, respectively. These results suggest that negative strand synthesis occurs after equimolar positive strand (A & B) packaging inside nascent virus particle. Molecular basis of the pathogenicity have been investigated in a second study. Very virulent IBDV strain (vvIBDV) can induce important clinical sign and mortality rates but no reliable molecular marker has been definitely identified yet. This study was carried out on a field strain (94432) which, in spite of being phylogenetically related to vvIBDVs, does not induce any mortality and only low morbidity in chickens. Using a reverse genetic system associated to 94432, several recombinant derived-94432 viruses were characterized in-vivo. Results demonstrated an important contribution of the polymerase encoded-segment B, especially of one amino acid at position 276, in the reduced pathogenicity of 94432. The biological function of amino acid 276 remains unknown
Kerestedjian, Jean-Jacques. "Traitement de l'infection expérimentale à "Rhodococcus equi" chez la souris nude". Paris 5, 1992. http://www.theses.fr/1992PA05P111.
Texto completoMenager-Marcq, Ingrid. "Etude du potentiel immunosuppresseur des lymphocytes t régulateurs CD8+CD28- dans un modèle murin de maladie inflammatoire chronique intestinale". Toulouse 3, 2006. http://www.theses.fr/2006TOU30176.
Texto completoLanaya, Hanane. "Rôle des cellules myéloïdes immatures GR1+CD11b+ dans le rejet du mastocytome P815". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210372.
Texto completoThe aim of our work was to define the mechanisms by which a single dose of cyclophosphamide (CTX), a chemical agent commonly used in chemotherapy treatment, induces the rejection of established P815 mastocytoma.
Our data show that CTX treatment leads to the selective loss of GR1medCD11b+ splenic myeloid cell producing TGF-â, a cytokine which is known to suppress antitumoral response. Furthermore, injection of CTX causes a decrease in the number of naturally occurring regulatory T cells (CD4+CD25+Foxp3+) in the spleen and the tumor. Finally, CTX treatment induces the differentiation of GR1highCD11b+ splenic myeloid cells into mature GR1highCD11b+CD11c+ (possibly dendritic cells?) which express high levels of CD11c, MHC class II and CD86 molecules. Of note, these cells are mainly detected in tumour necrosis areas.
Collectively, these results suggest that CTX prevents suppressive mechanisms and induces a population of CD11c+ myeloid cells which may present tumor antigens and activate T lymphocytes, an hypothesis in line with the requirement for CD4+ cells in CTX-induced long term resistance.
Doctorat en Sciences
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Ghisdal, Lidia. "Study of several acquired and genetic factors in relation with outcome in kidney transplantation". Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209606.
Texto completoLa survie du patient et du greffon se sont nettement améliorées depuis les débuts de la transplantation rénale. Les recommandations de pratiques cliniques basées sur l’évidence aident les cliniciens à améliorer la prise en charge standardisée des patients. Cependant, de nombreux programmes de recherche sont actuellement axés sur la découverte de biomarqueurs qui peuvent prédire les différents résultats chez les patients transplantés rénaux. Ces biomarqueurs sont nécessaires pour personnaliser la gestion et le traitement des patients.
Le but des travaux résumés dans cette thèse est d'évaluer l'impact potentiel de plusieurs facteurs biologiques acquis et génétiques spécifiques sur les résultats après la transplantation rénale, en particulier les facteurs de thrombophilie et les polymorphismes génétiques associés au diabète post-transplantation.
1. Facteurs de thrombophilie
Les patients en insuffisance rénale terminale présentent des anomalies complexes de la coagulation, dont les mécanismes sous-jacents ne sont pas connus à ce jour. La thrombose des vaisseaux du greffon et les événements thromboemboliques comme la thrombose veineuse profonde et / ou l’embolie pulmonaire sont des complications graves, mais relativement rares après transplantation rénale. Au cours de la dernière décennie, plusieurs études ont évalué l'impact des facteurs de thrombophilie sur les résultats après la transplantation rénale, tels que les événements thrombo-emboliques, y compris la thrombose de l’artère ou la veine du greffon, le rejet aigu, les événements cardiovasculaires ou la survie du greffon. Cependant, les limitations méthodologiques et l'hétérogénéité de ces études rendent les conclusions ou les recommandations difficiles. D’autre part, la prévalence exacte des facteurs de thrombophilie dans la population de patients en insuffisance rénale terminale et la correction éventuelle de ces facteurs après transplantation ne sont pas connues. Dans ce contexte, nous avons réalisé une étude prospective afin d’évaluer l’impact d’un panel de 11 facteurs de thrombophilie testés le jour de la transplantation et 1 mois plus tard, sur les événements thrombo-emboliques et le rejet aigu durant la première année de greffe [58]. Nous avons également évalué la prévalence de 7 facteurs de thrombophilie non-génétiques chez les patients en insuffisance rénale terminale et le taux de correction après la transplantation rénale dans une cohorte de 215 patients [59].
2. Diabète post-transplantation
Le diabète post-transplantation est une complication métabolique grave et fréquente après la transplantation. Les patients transplantés rénaux souffrant d’un diabète post-transplantation ont un risque plus élevé d'événements cardiovasculaires majeurs, de décès et d’échec de greffe. Une étude prospective rapporte une incidence de 20,5% durant les six premiers mois de greffe rénale, en utilisant les critères stricts de l'ADA (American Diabetes Association). La plupart des facteurs de risque identifiés sont communs avec le diabète de type 2 dans la population générale: l'âge, les antécédents familiaux, l’ethnie (africaine et hispanique), l'indice de masse corporelle élevé, une sérologie hépatite C positive et la présence d’un syndrome métabolique. Certains traitements immunosuppresseurs sont des facteurs de risque de diabète post-transplantation spécifiques et modifiables. Les inhibiteurs de la calcineurine sont diabétogènes et il a été clairement montré que le tacrolimus est plus diabétogène que la cyclosporine. En se basant sur ces données, nous avons remplacé le tacrolimus par la cyclosporine chez une série de patients ayant développé un diabète post-transplantation sous tacrolimus. Nous avons évalué rétrospectivement l’efficacité et la sécurité de cette approche [60]. Nous avons également élaboré des recommandations pour la prise en charge du diabète post-transplantation sur base de notre expérience et des études publiées [62].
La susceptibilité génétique du diabète post-transplantation a été étudiée par des approches «gènes candidats », mais les faibles effectifs et l'absence de réplication dans des cohortes indépendantes rendent les conclusions difficiles. Les études pan-génomiques de type « genome wide association study (GWAS) apportent un éclairage neuf sur les origines génétiques du diabète de type 2. Plus de 10 loci de susceptibilité ont été associés au diabète de type 2 dans la population générale, avec des odds ratio (OR) allant de 1.10 à 1.20, excepté un variant commun du gène TCF7L2 pour lequel le risque de la maladie augmente de 37% par allèle à risque. Nous avons utilisé une approche gène candidat en sélectionnant 11 variants génétiques associés au diabète de type 2 à travers ces GWAS et nous avons évalué leur association avec le risque de diabète post-transplantation durant les 6 premiers mois post-transplantation, dans une large cohorte de Caucasiens (N = 1076) [61].
Méthodologie générale
L’unité de transplantation rénale de l'Hôpital Erasme (Université Libre de Bruxelles) a créé une base de données clinique incluant les patients transplantés depuis 1964 dans l'institution et une biocollection (ADN et sérum) depuis 2001. En outre, depuis 2007, l'unité de transplantation rénale de l'Hôpital Erasme a développé une collaboration avec d'autres centres européens de transplantation rénale (CHU de Tours, CHU de Limoges, CHU de Brest, CHU de Saint-Étienne, CHRU de Lille, CHU de Poitiers et CHU de Bordeaux actuellement). Nous avons actuellement collecté les données cliniques et l’ADN de plus de 4000 receveurs d'allogreffe rénale.
Résultats
1. Facteurs de thrombophilie
Nous avons enrôlé prospectivement 320 greffes rénales consécutives correspondant à 317 patients greffés dans notre institution entre 2001 et 2006. Onze facteurs de thrombophilie ont étés dosés le jour de la transplantation. Dix patients ont étés exclus en raison de valeurs manquantes pour plus de 3 facteurs. Tous nos patients ont reçu de l’acide acétylsalicylique en prophylaxie, débuté juste avant la greffe. Le taux d'événements thromboemboliques et/ou de rejet aigu durant la première année post-transplantation (critère d’évaluation primaire composite) était de 16,7% chez les patients sans facteur de thrombophilie (N = 60) et de 17,2% chez ceux ayant au moins un facteur de thrombophilie (N = 250) (P=NS) le jour de la greffe. L'incidence du critère d’évaluation primaire était similaire chez les patients sans facteur de thrombophilie et ceux avec au moins deux (N = 135), ou au moins trois (n = 53) facteurs (16,3% et 15,1% respectivement, P=NS) et chez les patients avec au moins un facteur persistant 1 mois après la greffe (15,7%, P=NS). Aucun des facteurs de thrombophilie individuels présents le jour de la transplantation n’était associé au critère d’évaluation primaire. L'incidence des événements cardio-vasculaires à 1 an, la créatinine sérique à 1 an, la survie de greffe actuarielle à 4 ans n’étaient pas influencés par la présence d’au moins un facteur de thrombophilie le jour de la greffe (P= NS).
La prévalence des facteurs de thrombophilie était significativement plus élevée chez les patients dialysés que chez les patients non encore dialysés le jour de la greffe (74% vs 52,4%, P =0,03). La prévalence était similaire chez les patients hémodialysés et en dialyse péritonéale (P=NS). Un mois après la transplantation, la prévalence globale des facteurs de thrombophilie a chuté de 74,4% à 44,7% (P <0,001). La plupart des facteurs de thrombophilie avaient disparus après la transplantation.
2. Le diabète post-transplantation
Nous avons analysé rétrospectivement les paramètres du métabolisme glucidique chez 54 patients greffés rénaux traités par tacrolimus et développant un diabète post-transplantation. Trente-quatre patients ont été convertis à la cyclosporine alors que 20 patients ont poursuivi le tacrolimus (groupe contrôle). Après la conversion, le taux de rémission du diabète post-transplantation était de 42% (IC 95% :24-59%) 1 an après la conversion versus 0% dans le groupe contrôle (P=0,001). La conversion
était sûre en termes de fonction du greffon, de rejet aigu, de survie des patients et du greffon.
Dans notre étude multicentrique (Hôpital Erasme-Bruxelles, CHU de Tours, CHU de Limoges et CHRU de Lille), nous avons enrôlé 1477 patients greffés successivement. Parmi les 1229 patients éligibles pour l’étude, 1076 étaient Caucasiens (analyses primaires). Un total de 118 patients, soit 11% des Caucasiens ont développé un diabète post-transplantation durant les 6 premiers mois de greffe. En analyse multi-variée, le variant rs7903146 de TCF7L2 était indépendamment associé au diabète post-transplantation (OR = 1,60 pour chaque allèle T, P = 0,002). Les autres facteurs de risque indépendants étaient: l'âge du receveur, l’indice de masse corporelle au moment de la greffe, l'utilisation du tacrolimus et la survenue d'un épisode de rejet aigu traité par corticoïdes.
Conclusions
Les facteurs de thrombophilie sont très fréquents au stade terminal de l'insuffisance rénale et sont corrigés dans la grande majorité après la transplantation rénale. Cela suggère que la plupart des facteurs sont acquis et associés à l'urémie et / ou la dialyse. En outre, notre étude prospective n’a pas démontré d’impact des facteurs de thrombophilie détectés de manière systématique avant la transplantation sur les résultats après transplantation rénale, dans une population recevant un régime immunosuppresseur moderne et de l’acide acétylsalicylique en prophylaxie.
L’effet diabétogène du tacrolimus est réversible. Nos résultats suggèrent une amélioration significative du métabolisme glucidique après la conversion à la cyclosporine chez les patients transplantés rénaux atteints de diabète post-transplantation sous tacrolimus.
Le diabète post-transplantation et le diabète de type 2 partagent des facteurs de risque communs, dont un variant du gène TCF7L2. La place de ce type de biomarqueur dans la prédiction de la survenue du diabète post-transplantation et dans les stratégies de modification d’immunosuppression doit faire l’objet d’évaluations prospectives.
Doctorat en Sciences médicales
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Garzon, Edwin. "Etude immunopathologique de la maladie de Chagas chez la souris : rôle de la protéine immunosuppressive Tc52 et implications de la diversité génétique des souches de Trypanosoma cruzi dans l'expression de la virulence du parasite". Paris 6, 2004. http://www.theses.fr/2004PA066125.
Texto completoMarchand, Pascal. "Synthese et evaluation pharmacologique de derives indoliques a activites immunosuppressive et antitumorale (doctorat chimie therapeutique)". Nantes, 1999. http://www.theses.fr/1999NANT22VS.
Texto completoCordonnier, Julien. "Toxoplasma gondii : identification par docking inverse sur des cibles moléculaires de composés actifs issus de ressources naturelles". Electronic Thesis or Diss., Reims, 2024. http://www.theses.fr/2024REIMS001.
Texto completoTree barks, by-product of forestry industry, constitute an abundant and sustainable source of natural compounds. Toxoplasma gondii is the parasite responsible for toxoplasmosis, posing a threat to fetuses, newborns, and immunocompromised individuals. The current therapeutics, limited and poorly tolerated, are now confronted to chemoresistant phenomena. This doctoral project aims to explore the chemical space associated with tree barks from the Champagne-Ardenne region, as relevant protein targets to fight T. gondii. An initial in silico evaluation using reverse docking (AMIDEv2.0) was carried out to identify biological target for triterpenes derived from betulone, isolated from the European alder, which had exhibited in vitro anti-toxoplasmosis activity. Among 87 proteins of T. gondii, CDPK3 was identified as the most probable target. Subsequently, a bank of 25 essential 3D protein structures for parasite survival, including 19 homology-modeled structures, was compiled. Thereafter, compounds from the Essential National Chemical Library were screened against this protein bank, using AMIDEv2.0. Two proteins were identified as potential targets; one of them was ATG3, a protein structure modeled from homologs with less than 50% identity. Subsequently, the barks of European Larch, whose n-heptane extract had shown significant activity (58% inhibition of parasitic growth at 100 µg/ml), were subjected to a chemical profiling. First, through a fractionation process using Centrifugal Partition Chromatography, and then a dereplication approach combining data from nuclear magnetic resonance and mass spectrometry. Tools like VersaDB and CATHEDRAL were developed to facilitate the creation of custom-databases and assess the confidence level of annotations. 52 molecules were annotated and associated with a confidence score. Simultaneously, in vitro tests demonstrated that 2 out of the 12 CPC fractions, primarily composed of terpenic derivatives, inhibited the parasite's survival by more than 40% at 25 µg/ml. Ultimately, the annotated compounds from L. decidua were subjected to AMIDEv2.0. The overlap between in vitro and in silico results highlighted 7-oxo-dehydroabietic acid and daniellic acid, strongly correlated with the in vitro inhibitory activity of the barks. CDPK1 and the SET-containing Protein are likely protein targets for these two ligands, thereby providing initial insights into their mechanism of action. These two hits are currently undergoing in vitro evaluation to verify the efficiency of developed approach during this doctoral project
Gerard, Claire. "Développement d’une stratégie thérapeutique immunosuppressive dérivée de cellules myéloïdes dans la maladie du greffon contre l’hôte". Thesis, Bourgogne Franche-Comté, 2020. https://nuxeo.u-bourgogne.fr/nuxeo/site/esupversions/a02d57d7-6368-477d-8e8d-0badac13bda0.
Texto completoAbstract :Our team has developed an original cell therapy derived from monocytes. This sub-population of human suppressor cells of myeloid origin, called Human Monocyte-Derived Suppressor Cells (HuMoSC, CD33+ cells) is able to inhibit effector T cell proliferation and to induce CD4 and CD8 Treg. It has been demonstrated that HuMoSC prevent from graft-versus-host disease (GvHD).In a first time, we showed that an inflammatory environment or the presence of immunosuppressive drugs did not decrease HuMoSC abilities to inhibit T cell proliferation and to promote CD4 and CD8 Treg induction. Finally, we showed that graft-versus-leukemia (GvL) effect is preserved in presence of HuMoSC. Taken together, those data confirm the interest of HuMoSC in GvHD prevention.Nevertheless, due to a low yield of HuMoSC generation with this protocol and problem with avaibility of CD33 GMP beads, we also modified our protocol to isolate CD14+ cells, called CD14-HuMoSC. This is why in a second time, we took interest in HuMoSC and CD14-HuMoSC supernatant properties. These protocol modifications allow us to obtain large number of CD14-HuMoSC cells and large quantities of supernatant produced under GMP conditions. We showed that both supernatants decrease T cell activation and proliferation, decrease Th1 response in favor of Th2 response, promote Treg induction and decrease capacity of dendritic cells to induce T cell proliferation. In vivo, supernatants prevent from GvHD in a murine model of xenogenic GvHD. Finally, in order to assess that these supernatants will be efficient in patient, we showed that an inflammatory environment or presence of immunosuppressive drugs did not alter both supernatant immunosuppressive effects. These results confirm their therapeutic interest. Proteomic analysis allowed us to identify immunosuppressive proteins which could be responsible for supernatants immunosuppressive capacities.In conclusion, HuMoSC and supernatant derived from HuMoSC represent a promising therapeutic arsenal for GvHD prevention but also in inflammatory diseases
Néel, Cécile. "Epidémiologie du virus de l'immunodéficience simienne chez les gorilles : prévalence et transmission du SIVgor chez les gorilles en milieu naturel au Cameroun". Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20095/document.
Texto completoSIV infecting chimpanzees and gorillas are the precursors of the Human Immunodeficiency Virus type 1. The four groups of HIV-1 are the results of four different viral transmissions from apes to humans. Using non invasive methods we discovered the reservoir of HIV-1 M and N in two communities of chimpanzees (Ptt) in Cameroon and found that Gorillas (Ggg) are infected by a SIV close to HIV-1 O and P. While SIVgor has not yet been detected in chimpanzees, phylogeny shows that Ptt transmitted this virus to Ggg. Using a multidisciplinary approach, we studied the characteristics of the infection in wild living gorillas. We prospected 13 sites in Cameroon and 3 in CAR. 2120 fecal samples of gorillas and 442 of chimpanzees were collected. SIVgor infection was detected in 3 sites in Cameroon and the prevalence ranges from 3.2% to 4.6%, lower than in chimpanzees. Several social groups of gorillas with overlapping home-ranges were infected and the prevalence within group could exceed 25%. Viruses of the same group are genetically close, showing epidemiologic links. In a follow up study between 2004 and 2009 on one site, we discovered a focus of infection with 2 cases of seroconvertion and we re-sampled one infected female 5 years after. In this site, the prevalence of SIVgor is stable and the number of infected females is higher than the males. The social structure of gorillas and their behavior can partly explain for the repartition and prevalence of SIVgor, as well as the differences with the infection in chimpanzees. This multidisciplinary study proves the feasibility of a follow up study in wild living gorillas. If SIVgor turns out to be pathogenic, a follow up will be essential for this endangered species
Dong, Yuan. "Implication des polynucléaires neutrophiles au cours de la maladie d’Alzheimer et des tauopathies Neutrophil hyperactivation correlates with Alzheimer's disease progression Reduced Oxidative Burst by Primed Neutrophils in the Elderly Individuals Is Associated With Increased Levels of the CD16bright/CD62Ldim Immunosuppressive Subset". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS445.
Texto completoNeutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. Our study demonstrated that blood samples from Alzheimer’s Disease (AD) patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species (ROS) production and increased levels of intravascular neutrophil extravascular traps. The homeostasis of circulating neutrophils in these patients also changed: the ratio between the harmful hyperreactive CXCR4high/CD62Llow senescent and the CD16bright/CD62Ldim immunosuppressive neutrophil subsets rose in the latter stage of the disease. These abnormalities, that may play an instrumental role in establishing systemic chronic inflammation, were greater in fast-decliner than in slow-decliner patients. Some abnormalities, including the increased level of ROS production, were observed in patients with atypic AD but not in Tauopathies suggesting that these alterations are specific of amyloid pathology. Our data strongly suggest that the neutrophil phenotype may constitute an innovative and prognostic blood biomarker in patients with Alzheimer’s disease open new perspectives for the development of innovative immunotherapy strategies based on neutrophil modulation
Gonçalves, Da Silva Angela. "La maladie de Marek : recherche d'une nouvelle possibilité de protection utilisant une protéine purifiée". Tours, 1987. http://www.theses.fr/1987TOUR4007.
Texto completoOuaguia, Laurissa. "Rôle des lymphocytes T régulateurs humains dans l'échappement de la maladie associée à l'infection par le virus de l'hépatite C". Thesis, Lille 1, 2015. http://www.theses.fr/2015LIL10117/document.
Texto completoHepatitis C is characterized by a high risk of chronicity. Our team described the involvement of natural and induced regulatory T lymphocytes (Treg and iTreg) in the worsening of the disease. However, the specific impact of HCV on these 2 regulatory populations remains unclear. Our hypothesis is that HCV worsens the immunosuppressive environment by (i) promoting intrahepatic recruitment of Treg, (ii) increasing their suppressive phenotype and activity, and (iii) inducing the emergence of iTreg.In the first part of my thesis, I showed an increased intrahepatic frequency of Treg and iTreg correlated to the worsening of hepatitis C into cancer in a patient.In the second part, I showed for the first time that HCV was able (i) to internalize human Treg, (ii) potentiate their regulatory phenotype, (iii) increase their suppressive function, (iv) stimulate their proliferation and (v) induce the secretion of proinflammatory factors that can promote disease chronicity. I also showed that HCV increases the intrahepatic recruitment of Treg.In the third part, I showed that HCV can promote the emergence of iTreg which can efficiently suppress the immune response.My findings suggest that HCV promotes the intrahepatic recruitment of Treg cells, increases their regulatory phenotype and potentiates their suppressive activity. Very interestingly, I’ve also showed that HCV uptakes may promote hepatic inflammation by Treg cells. Finally, HCV seems to favor the emergence of induced regulatory cells. Taken together, these results strongly suggest that HCV increases the hepatic immunosuppressive environment and this may explain, at least partly, how the HCV escapes from the immune response
Berthault, Camille. "Etude des mécanismes menant à l'atrophie des organes lymphoïdes primaires dans le cadre de l'infection précoce par le virus de la maladie de Marek chez la poule". Thesis, Tours, 2017. http://www.theses.fr/2017TOUR4023.
Texto completoMarek's disease virus (MDV) infection induces early and transient immunosuppression associated with atrophy of the thymus (TA) and the bursa of Fabricius (BA) in chicks. The aim of this work was to better understand the cellular mechanisms responsible for this atrophy. The first step in my work was to establish an in vivo infection model leading to a sufficient and reproducible BA and TA. Once established, this model allowed us to study the effect of MDV in these organs at 6, 10 and 14 days post-infection. The results indicate that apoptosis and inhibition of proliferation can contribute to BA, whereas only the increase in apoptosis leads to TA. The lymphocyte blood count showed a decrease in B-lymphocytes during the first 2 weeks of infection that seems related to BA. This technique therefore seems a promising non-invasive tool to diagnose BA at early times of MDV infection. A difference in sensitivity to MDV-induced TA and BA was found in two lines White Leghorn of different B haplotype, both of which very sensitive to tumor development
Mansi, Laura. "Intégration de l’analyse de l’immunomodulation induite par les inhibiteurs de mTOR dans leur développement en cancérologie". Thesis, Bourgogne Franche-Comté, 2017. http://www.theses.fr/2017UBFCE012.
Texto completoThe key role of the mTOR (mammalian Target of Rapamycin) pathway in cellular homeostasis raises a real interest in many therapeutics areas. Inhibitors of mTOR (mTORi) are used for graft rejection prevention to inhibit the T lymphocyte (LT) activation and induce regulatory T cells (LTreg). In cancerology, they are used for their antiproliferative and antiangiogenic actions. However, the clinical efficacy of those treatments is low. Although several mTORi resistance mechanisms linked to the tumor cell have been identified, their impact on the immune system appears as a key factor in their efficiency. Thus, our hypothesis is that the clinical efficacy of mTORi could also be dependent of an anti-tumoral immunity modulation resulting from those treatments.We performed an immunomonitoring of the Treg rate and the tumor specific Th1 anti-tumor response among a prospective cohort of patients with a metastatic renal carcinoma treated by everolimus (mTORi). We observed that the Treg rate and the suppressive function increase after the second month of treatment for almost all the patients. Paradoxically, an increase of the Th1 anti-tumoral response has also been observed for these patients. At disease progression, a majority of the patients has shown an important increase of Treg with a decrease of the Th1 response. Thus, we have been able to define different immune profiles based on the modulation of these two parameters. Progression free survival of patients with an earlier decrease of Treg and an increase of Th1 response was significantly longer compared to other patients (13.2 vs 4 months p=0.02). This immunomodulation has been consistently confirmed with patients affected by neuroendocrine tumor and treated with everolimus. The treatment impact on Treg and the Th1 response was not related to the pharmacokinetic of the drug. Thereafter, we have studied in vivo the impact of mTORi on the anti-tumoral immune response with mice affected by different tumors. We have observed the same increase of Treg in mice treated with mTORi as the increase observed in the patients. Thus, using antibodies depleting the Treg or transgenic mice allowed us to confirm the deleterious role of Treg on the anti-tumor mTORi efficacy. Those results strongly suggest that mTORi have a double effect on the immune system, a harmful impact by the induction of an immunosuppressive environment and a positive impact by the increase of the anti-tumor Th1 response.In a second time, we have studied the positive effect of mTORi on the immune system in order to optimize the anti-tumoral immunotherapies. We have shown that the administration of temsirolimus (mTORi) improves the anti-tumoral efficiency of a therapeutic vaccination on mice. Indeed, the synergic effect of this combination is tied with an augmentation of tumor infiltrate anti-tumor T CD8 with a central memory phenotype. The efficiency of this combination has been greatly improved by the addition of an antagonist CCR4 allowing the elimination of Treg generated by temsirolimus.In conclusion, mTORi remain a promising strategy in cancerology even if their use is likely to be reduced as new immunotherapies such as checkpoint inhibitors (renal carcinoma) or other targeted therapies (cycline dependent kinase inhibitors in breast cancer) appeared. In the future, the development of mTORi must integrate biomarkers taking into account the impact of these treatments on the immune system, and therapeutic combination such as the immunotherapy
Bah, Ramatoulaye. "Les immunoglobulines intraveineuses et la réponse spécifique des cellules T dans la prévention de la maladie lymphoproliférative post-greffe associée au virus Epstein-Barr chez les enfants greffés de cellules souches hématopoïétiques". Thèse, 2015. http://hdl.handle.net/1866/13540.
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