Thesis (MScMed)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: The aim of this study was to investigate the effect of MBV and Coley’s Toxin on dendritic cells in vitro. The dendritic cell system of antigen presenting cells is the initiator and modulator of the immune response. The principle function of the dendritic cells is to present antigens to resting naïve T lymphocytes: these cells are the only APCs that prime naïve T cells and only mature DCs can carry out this function.Previous studies done on dendritic cells showed that bacterial peptides can induce the maturation of dendritic cells. With the results of these studies in mind we hypothesized that these two vaccines will also induce the maturation of dendritic cells. Chapter 1 is a literature review on the immune system explaining the organs and cells of the immune system. Chapter 2 includes a full description of DCs, the MBV and Coley’s toxin. Also included in this chapter is a short explanation of the principle of the technique being used for the identification and maturation of both mDCs and pDCs, namely the technique of flow cytometry. Chapter 3 describes the method for the phenotypic identification of DCs: the subsets are distinguished by their absence of expression of several lineage markers for lymphocytes, monocytes and NK cells and the expression of CD11c (in the case of myeloid DCs) and CD123 (in the case of plasmacytoid DCs). The inclusion of HLA-DR in addition to the previous described markers allows the discrimination of CD123+ DCs from basophils. The assay requires three tubes per sample which enables quick analysis of these rare subsets with a small sample volume. This assay was applied to peripheral blood samples obtained from healthy individuals and individuals with cancer, HIV and HIV and TB co-infected patients. Our results showed that the maturation status of DCs in HIV and lymphoma were low but those measured in the case of HIV + TB patients were even higher than in the control group. Chapter 4 and 5 describe the in vitro activation and maturation status of DCs following their incubation with bacterial-derived products. Interactions between DCs and microbial pathogens are fundamental to the generation of innate and adaptive immune responses and upon contact with bacteria or bacterial components such as lipopolysaccharide (LPS), immature DCs undergo a maturation process that involves expression of costimulatory molecules, HLA molecules, and cytokines and chemokines, thus providing critical signals for lymphocyte development and differentiation. In this study, we investigated the response of human DCs to MBV and Coley’s Toxin. Previous studies showed DCs can be activated with killed Streptococcus pyogenes. With this study in mind it was hypothesized that the MBV and Coley’s Toxin used in this study might modulate DC maturation. The results of this study showed that the MBV and Coley’s toxin did induce the maturation of both pDCs and mDCs as measured by increased surface expression of costimulatory molecules such as CD80 and CD83. Chapter 6 presents the measurement of cytokines released after the PMBCs had been were incubated with Coley’s Toxin and Mixed Killed bacteria. The BD™ Cytometric Bead Array (CBA) flex set was used for the simultaneous detection of multiple soluble analytes. The results indicated that both Coley’s Toxin and the MBV activated the DCs and subsequently induced TH1 as well as a TH2 responses in the T cells present in the cell cultures. Finally, a general conclusion discussing the significance and implications of our results as well as possible future research required is discussed in Chapter 7. DCs are potent antigen presenting cells (APCs) which play a critical role in the regulation of the immune response. There is great interest in exploiting DCs to develop immunotherapies for cancer, chronic infections, immunodeficiency diseases and autoimmune diseases. / AFRIKAANSE OPSOMMING: Die doel van die studie was om die effek van ‘n gemengde bakteriële vaksiene en Coley se toksiene op dendritiese selle te toets in vitro. Die dendritiese sel sisteem speel ‘n belangrike rol in die modulering en reaksie van die immuun sisteem.Die hoof funksie van dendritiese selle is om antigene bloot te stel aan naïewe ongeaktiveerde T selle. Slegs volwasse dendritiese selle kan die T selle aktiveer. Vorige studies het bewys dat bakteriële peptiedes die veroudering van die dendritiese selle kan induseer. Met die resultate in gedagte het ons gehipotiseer dat die twee vaksienes ook die maturasie van dendritiese selle kan induseer. Hoofstuk 1 is ‘n literatuur studie wat handel oor die organe en selle van die immuun sisteem. Hoofstuk 2 gee n volle beskrywing van dendritiese selle, die gemengde bakteriële vaksiene en Coley se toksiene. Ingesluit in die hoofstuk is die beskrywing van die prinsiep van die tegniek, vloei sitometrie, wat gebruik word vir die identifikasie en veroudering status van die dendritiese selle. Hoofstuk 3 beskryf ‘n vloei sitometrie metode vir die fenotipiese identifikasie van dendritiese selle. Dendritiese sel tipes kan onderskei word deur die afwesigheid van sekere merkers vir limfosiete, monosiete en NK selle. Plasmasitoïede dendritiese selle druk CD123 uit en miloïede dendritiese selle druk CD11c uit. HLA DR is ook ingesluit saam met die bogenoemde merkers om die dendritiese selle te onderskei van basofiele. Vir elke toets word slegs drie buise geprosesseer en dus kan die subklasse vinning geanaliseer word. ʼn Klein volume bloed word benodig vir die toests. Perifêre bloed is gebruik vir die toets op bloed monsters van 10 gesonde individue en individue met kanker, HIV en HIV en TB. Die resultate van die studie het getoon dat die maturasie status van die dendritiese selle in HIV en limfoom was, maar in die geval van HIV en TB pasïente was die maturasie status selfs hoër as die van die kontrole groep. Hoofstuk 4+5 beskryf die aktivering en maturasie status van die dendritiese selle na inkubasie met die bakteriële produkte. Interaksie tussen dendritiese selle en patogene speel ‘n belangrike rol in die aktivering van die immuunstelsel. Wanneer dendritiese selle in aanraking kom met bakterieë of bakteriële komponente, matureer die dendritiese sel wat lei tot the uitdrukking van stimulerings molekules, HLA molekules end die uitskeiding van sitokiene. Die uitdrukking van die molekules lei tot limfosiet ontwikkeling en differensiasie. In die studie het ons gekyk na die reaksie van menslike dendritiese selle in die teenwoordigheid van die gemende bakteriële vaksiene en Coley se toksiene. Vorige studies het bewys dendritiese selle word geaktiveer deur Streptococcus pyogenes. Met die resultate in gedagte het ons gehipotetiseer dat die gemengde bakteriële vaksiene en Coley se toksiene ook die maturasie van dendritiese selle kan induseer. Die resultate van die studie het bewys dat die gemengde bakteriële vaksiene en Coley se toksiene die veroudering van beide pDCs en mDCs induseer. Die uitdrukking van verouderings merkers CD80 en CD83 is gemeet. Hoofstuk 6 beskryf ‘n vloei sitometrie metode om die sitokiene te meet wat afgeskei word nadat selle geinkubeer het in die teenwoordigheid van Coley se toksiene en die gemengde bakteriële vaksiene.Die BDTM CBA Flex set metode het dit moontlik gemaak om meer as een sitokiene te meet in net een buis Die resultate het getoon dat albei die vaksienes ‘n TH1 en TH2 reaksie veroorsaak. Laastens volg‘n algemene afleiding waar ons kyk na die toepassing en implikasies van die resultate asook toekomstige navorsings moontlikhede,word bespreek in Hoofstuk 7 Dendritiese selle speel ‘n kritiese rol in die regulering van die immuun reaksie. Verdere studies kan nou gedoen word om dendritiese selle terapeuties toe te pas vir die behandeling van kanker, autoimmuniteit, immuun onderdrukkende siektes en kroniese siektes.

The purpose of this study was to separate acute and chronic effects of moderate exercise on the immune system by analyzing three sets of experimental and control groups; (1) 72 hours, (2) 1 week, (3) 2 weeks post exercise. Mice swam 5 days per week for 3 weeks accumulating a total of 125, 225, and 225 minutes of exercise in weeks 1, 2, and 3, respectively. Moderate swimming exercise did not result in a significant increase in SDH levels (p > 0.05). There was no change in tissue cell responses as measured by mitogen responsiveness, nor in splenic and thymic cell counts in response to the training regimen at any time point (p ≥ 0.05). Total, CD4, CD8, and T cell counts in the lymph nodes were significantly suppressed at 72 hours and 2 weeks post exercise (p ≤ 0.05). It appears that chronic exercise resulted in an increased trafficking of lymphatic cells, which could be interpreted as a sign of heightened immune reactivity.

No description available.

Thesis (MScMedSc) -- Stellenbosch University, 1998. / Bibliography / ENGLISH ABSTRACT: There is a progressive maturation of the immune system from infancy to adulthood. The immature immune system in early life is characterised by impaired macrophage function and antigen presentation as well as a higher naIve to memory T cell ratio with subsequent diminished IFN-y production. Children with tuberculosis often present with lymphadenopathy, the complications thereof or with systemic spread of the organisms. Adults generally manifest with pronounced systemic effects (such as weight loss and high fever) and immunopathology (such as cavitation and fibrosis). We hypothesised that the immunopathology in adults may be due to enhanced cytokine production in comparison to children. The first aim of this study was therefore to measure cytokine responses in healthy children and adults. Cytokine responses in patients with tuberculosis will be examined in future studies. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood obtained from 9 healthy children and 9 healthy adults. The cells were cultured in serum-free medium, unstimulated or polyclonally stimulated with Phytohaemagglutinin (PHA). Supernatants were harvested after which IFN-y, IL-2, TNF-a., IL-4 and IL-IO production was determined by means of ELISA analysis. Ri'J"A was ~ubsequently extracted from the cells followed by RT-PCR analysis for the semiquantitative determination of mRNA levels of these cytokines. PBMC isolated from healthy children produced significantly less IFN-y protein than adults. Futhermore, IFN-y production in the adults seemed to be trimodally distributed. No significant differences could be found in the production of IL-2, TNF-a, IL-4 and IL-] O. Although children produced low levels of IFN-y protein, their IFN-y, TNF-a, IL-2, IL-4 and IL-IO mRNA levels were comparable to that of adults. Tuberculosis is a major cause of mortality and morbidity, particularly in the third world. Ravensmead and Uitsig, two adjacent suburbs in the Western Cape, have a tuberculosis incidence of> I 000/100000 population. Also, up to 90 % of the children in the Western Cape have been reported to be infested by intestinal parasites such as Ascaris lumbricoides and Trichurius trichl/ria. Infection with M tuberculosis indut:es a Th 1 Stellenbosch University http://scholar.sun.ac.za iv In:.,c response, while intestinal parasites elicit a Th2 immune response. Th2 dominance induced by intestinal parasite infestations could predispose individuals to an enhanced susceptibility to M. tuberculosis. The second aim of this study was to investigate serum IgE levels, surrogate markers for Th2 activation, in the community. The serum 19B levels were subsequently correlated to the tuberculosis incidence per enumerator sub-district (ESD), crowding, female literacy and socio-economic levels. Similarly, the tuberculosis incidence per ESD was correlated with the above mentioned parameters. A significant positive correlation was found between tuberculosis incidence and the serum 19E levels in the community. However, further studies are needed to determine if intestinal parasites are the main cause of the high 19B levels in the community and to dCh111ine if parasite loads or Th2 dominance are causally linked to the incidence of tuberculosis. Correlation between serum 19E levels and tuberculosis incidence with the other parameters were significant, except in the case of crowding. The third aim of this study was to measure serum IgE and specific 19E levels against Ascaris and common allergens on presentation of tuberculosis and again after completion of successful treatment. Significant declines in serum 19B and Ascaris specific 19B levels were observed after completion of tuberculosis treatment. This down regulation of IgE levels may be due to an up regulation of ThI responses in patients following successful treatment for tuberculosis. / AFRIKAANSE OPSOMMING: Die immuunsisteem matureer toenemend vanaf kinderjare tot en met volwassewording. Die onvolwasse immuunsisteem van jong kinders word gekenmerk deur verswakte makrofaag-funksionering en antigeenpresentering, sowe) as 'n verhoogde naiwe tot geheue T-sel verhouding met gevolglikc verminderde IFN-y produksie. Kinders met tuberkulose presenteer gewoonlik met Iimfadenopatie, komplikasies daarvan of met gedissemineerde siekte. Volwassenes presenteer met sistemiese gevolge (soos gewigsverlies en hoe koors) en immunopatologie (soos kavitasie en fibrose). Ons hipotese is dat die immunopatologie in volwassenes die gevolg is van 'n verhoogde sitokienproduksie in vergelyking met kinders. Die eerste doelwit van die studie was om sitokienproduksie in gesonde kinders en volwassenes te meet. Sitokienproduksie in tuberkulose pasiente sal in 'n opvolgstudie bepaal word. Perifere bloed mononukleere selle was geisoleer vanuit heel bloed verkry vanaf 9 gesonde kinders en 9 gesonde volwassenes. Die selle was gekweek, ongestimuleer of gestimuleer met Phytohaemagglutinien (PHA). Supernatante was geoes vir die bepaling van IFN-y, IL-2, IL-4, IL-I0 en TNF-a. produksie, deur gebruik te maak van ELISA analise. RNA was gevolglik vanaf die selle ge-ekstraheer vir die tru-transkriptase polimeerketting reaksie analise, waartydens sitokien mRNA vlakke op 'n semi-kwantitatiewe wyse bepaal was. Perifere bloed mononukleere selle geisoleer vanaf die kinders het minder IFN-y geproduseer as die van volwassenes. Hierdie verminderde produksie was hoogs betekenisvol. Dit wou voorkom asof die IFN-y produksie deur volwassenes trimodaal versprei was. Geen betekenisvolle verskille tussen kinders en volwassenes kon gevind word in die produksie van IL-2, IL-4, IL-IO en TNF-a nie. Alhoewel kinders minder IFN-y proteien geproduseer het, het hulle IFN-y, IL-2, IL-4, IL-JO en TNF-a mRNA produksie met vlakke van volwassenes ooreengestem. Tuberkulose speel 'n groat rol in morbiditeit en mortaliteit in veral die derde wereld. Ravensmead en Uitsig, twee aangrensende voorstede in die Wes-Kaap, het 'n tuberkulose voorkomssyfer van> 1 000/1 00000 populasie. Verder, is tot 90 % van die kinders in die Stellenbosch University http://scholar.sun.ac.za VI Wes-Kaap gei'nfesteer met intestinale parasiete soos Ascaris Ilimbricoides en Trichllrills trichllria. M. tuberculosis infeksie induseer 'n Thl immuunrespons, terwyl intestinale parasiete 'n Th2 immuunrespons uitlok. 'n Dominante Th2 respons mag moontlik individue predisponeer tot 'n verhoogde vatbaarheid vir M. tuberculosis. Gevolglik was die tweede doelwit van die studie om serum IgE vlakke as surrogaat merkers vir Th2 aktivering in die gemeenskap bestudeer. Die serum IgE vlakke was gevolglik gekorreleer met die tuberkulose voorkoms per opnemerssensusgebied (OSG), saamdringing, vroulike geletterdheid en sosio-ekonomiese vlakke. Die tuberkulose voorkoms per OSG, is op dieselfde wyse gekorreleer met die bogenoemde parameters. 'n Betekenisvolle positiewe korrelasie is gevind tussen tuberkulose voorkoms en serum IgE vlakke in die gemeenskap. Verdere stuciies is egter nodig om te bepaal of intestinale parasiete weI die oorsaak van die hoe IgE vlakke in die gemeenskap is en of parasiet ladings of Th2 dominansie oorsaaklik verbind kan word aan die tuberkulose voorkoms. Die derde doelwit van die studie was om serum 19E en spesifieke IgE vlakke teen Ascaris en algemene allergene te meet met presentering van tuberkulose en weer na voltooing van suksesvolle behandeling. 'n Betekenisvolle afname in serum 19E en Ascaris spesifieke 19E vlakke is waargeneem na vohooing van tuberkulose behandeling. Die afregulering van 19E vlakke kan moontlik toegeskryf word aan die opregulering van Th1 response in pasi"ente na voltooing van suksesvolle behandeling van tuberkulose.

by Stefanie P.C. Czerwinski. / Thesis (M.S.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader. / Sjèogren's Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today's therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17(Sb (Bestradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL- 1\U+fffd\, TNF-a, IFN-(Sd(B, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1\U+fffd\ TNF-a, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels.

Thesis (Ph.D.)--Mississippi State University. College of Veterinary Medicine. / Title from title screen. Includes bibliographical references.

Fruit and vegetables are often spoilt during storage, handling and transportation due to microorganisms. The common spoilage causes are fungi within the order Mucorales, the largest order of the class Zygomycetes. Such spoilage can result in reduced food supplies, poor quality and severe losses to producers and traders. The study was to investigate the type of Mucorales prevalent in various commodities and in a particular market than others. Fifty infected papaya, peaches and strawberries were collected at five occasions from large, medium and small markets. Isolation was done aseptically in a biosafety cabinet. Mucorales were identified morphologically, through culture based tests and molecular techniques. Mucorales isolated are Rhizopus stolonifer, Mucor circinelloides and Mucor racemosus. Mucorales were isolated at a higher rate in samples collected from the small market than other two markets. Spoilage in all three markets is assumed to be influenced by lack of modified temperatures in the storage room. / Life and Consumer Sciences / M. Sc. (Life Sciences)

Fruit and vegetables are often spoilt during storage, handling and transportation due to microorganisms. The common spoilage causes are fungi within the order Mucorales, the largest order of the class Zygomycetes. Such spoilage can result in reduced food supplies, poor quality and severe losses to producers and traders. The study was to investigate the type of Mucorales prevalent in various commodities and in a particular market than others. Fifty infected papaya, peaches and strawberries were collected at five occasions from large, medium and small markets. Isolation was done aseptically in a biosafety cabinet. Mucorales were identified morphologically, through culture based tests and molecular techniques. Mucorales isolated are Rhizopus stolonifer, Mucor circinelloides and Mucor racemosus. Mucorales were isolated at a higher rate in samples collected from the small market than other two markets. Spoilage in all three markets is assumed to be influenced by lack of modified temperatures in the storage room. / Life and Consumer Sciences / M. Sc. (Life Sciences)

La réponse immune représente une réponse complexe à laquelle correspond une succession d’événements orchestrés finement. Parmi les mécanismes qui régulent la réponse immune, les lymphocytes T régulateurs (Tregs) assurent le maintien de la tolérance en périphérie et le contrôle des réponses immunes adaptatives. Ils représentent une population hétérogène et leurs mécanismes de suppression sont toujours l’objet d’intenses recherches. Suivant le contexte de suppression et leur nature, les lymphocytes Tregs réalisent une inhibition de l’activation des lymphocytes Th, soit directement, soit via la modulation de la fonction des cellules dendritiques (DC). <p>Dans un modèle d’immunisation par des cellules dendritiques chargées de KLH, les lymphocytes Tregs naturels contrôlent sélectivement l’initiation des réponses de type Th1/CTL spécifiques de l’antigène. Le but de ce travail était de définir quels sont les acteurs potentiels du contrôle de cette réponse. A l’aide de l’anticorps PC61 dirigé contre le récepteur CD25 et éliminant les lymphocytes Tregs naturels, nous avons montré que le ligand de costimulation CD70 joue un rôle clé dans leur régulation de la réponse Th1/CTL (Article 1). Ainsi, dans des conditions normales, la cytokine IL-12 induit principalement l’initiation de la réponse Th1 in vivo, tandis qu’en l’absence de lymphocytes Tregs naturels, la voie CD70/CD27 est une voie alternative d’induction de l’IFN-γ. Cette voie d’activation pourrait être opérationnelle dans certains contextes infectieux lorsque les lymphocytes Tregs sont déstabilisés voire éliminés, par exemple lors d’infections par Toxoplasma gondii ou par les virus HTLV1, SIV ou HIV. Nous avons montré que les lymphocytes Tregs naturels diminuent l’expression du ligand CD70 sur les DC, de manière dépendante de son récepteur CD27. <p>Ensuite, nous nous sommes intéressés à une deuxième population de lymphocytes T régulateurs, les lymphocytes Tregs ICOShigh induits in vivo par le traitement avec l’anticorps anti-CTLA-4. Dans le cadre d’une colite induite par l’agent alkylant TNBS et mettant en jeu une réponse Th1, cette population de lymphocytes Tregs amplifiée par le traitement à l’anticorps anti-CTLA-4 régule la réponse immune via la cytokine anti-inflammatoire IL-10 et l’enzyme immunosuppressive IDO (Article 2). Ainsi, les résultats obtenus nous ont permis de répondre à notre objectif et de définir certains mécanismes de suppression des lymphocytes Tregs naturels et des lymphocytes Tregs induits. <p>Dans la dernière partie de ce travail, nous avons cherché à comparer les populations de lymphocytes Tregs naturels et ICOShigh présentes dans l’intestin d’une souris naïve. Une analyse transcriptomique a révélé que ces deux populations s’opposent sur les plans phénotypique et fonctionnel. Nous proposons un modèle dans lequel les deux populations de lymphocytes Tregs agiraient en synergie pour maintenir l’homéostasie intestinale. Les lymphocytes Tregs ICOShigh différenciés au niveau local et continuellement activés contrôleraient la réponse inflammatoire associée à la présence de la flore commensale. Les lymphocytes Tregs naturels, en quiescence dans les ganglions mésentériques, n’interviendraient qu’en cas d’infection par des pathogènes.<p>L’étude des lymphocytes T régulateurs soulève un certain nombre de concepts clés de l’immunité :la spécificité des réponses, la distinction des microorganismes commensaux et pathogènes… Mieux connaître les lymphocytes Tregs dans un modèle murin permettra de mieux comprendre les réponses inflammatoires intestinales chroniques observées chez l'homme et d’envisager, à terme, de nouveaux traitements.<p>/<p>An immune response is complex and implies numerous sequential events. It is regulated by different mechanisms, among which regulatory T cells maintain peripheral tolerance and control adaptive immune responses. Regulatory T cells are very heterogeneous and suppress immune responses through different mechanisms, still under investigation. They can inhibit T cell activation directly or through the modulation of dendritic cell function, depending on their nature and the tissular context.<p>In a dendritic cell-mediated immunization model, naturally occurring regulatory T cells selectively control the priming of antigen-specific Th1/CTL responses. Our goal was to define the potential actors of this control, targeted by natural regulatory T cells. Using the PC61 antibody which targets and depletes these cells, we showed that the costimulation ligand CD70 plays a key role in their control of Th1/CTL responses (first article). We showed that mainly IL-12 provokes Th1 development in normal conditions, wheras CD70 plays a major role in priming Th1 responses in the absence of natural Tregs. This pathway can be operational if regulatory T cells are destabilized or even depleted, for example during infection with Toxoplasma gondii or with HTLV1, SIV or HIV. We showed that natural Tregs downregulate CD70 expression on the surface of DCs.<p>Next, we focused on another regulatory T cell population, induced in vivo by the anti-CTLA-4 mAb treatment. In a model of pro-Th1 colitis, induced by the alkylating agent TNBS, these ICOShigh regulatory T cells exert an IL-10 and IDO-dependant control over the immune response (second article). Thus, we succeeded in determining some control mechanisms of the immune response targeted by two populations of regulatory T cells.<p>Finally, we compared two regulatory T cell populations: naturally occurring regulatory T cells and ICOShigh regulatory T cells from the intestines of naïve mice. A transcriptional analysis revealed two populations phenotypically and functionally distinct. We proposed a model in which these populations act synergistically and both maintain intestinal homeostasis. ICOShigh regulatory T cells might control commensal gut flora-specific inflammatory responses and quiescent natural regulatory T cells from mesenteric lymph nodes might control potential pathogen infections.<p>As a conclusion, this study raises some immunological issues: specificity of immune responses, distinction between commensal and pathogenic microorganisms… A better knowledge of these regulatory populations will lead to a better understanding of human intestinal responses and in the medium term will lead to new therapeutic approaches and tools.<p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished