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1
Ye, Song Cheung H. Tak. "Identification of a thymic extracellular matrix protein that promotes strong thymocyte adhesion". Normal, Ill. Illinois State University, 1990. http://wwwlib.umi.com/cr/ilstu/fullcit?p9115234.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--Illinois State University, 1990.Title from title page screen, viewed December 2, 2005. Dissertation Committee: H. Tak Cheung (chair), Herman Brockman, Harry Huizinga, Anthony Otsuka, Brian Wilkinson. Includes bibliographical references (leaves 116-127) and abstract. Also available in print.
2
Wang, Min-Guang Cheung H. Tak. "Identification of an extracellular matrix epitope involved in T cell adhesion". Normal, Ill. Illinois State University, 1992. http://wwwlib.umi.com/cr/ilstu/fullcit?p9311292.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--Illinois State University, 1992.Title from title page screen, viewed February 7, 2006. Dissertation Committee: H. Tak Cheung (chair), Mathew J. Nadakavukaren, Alan J. Katz, Brian J. Wilkinson, Lynne A. Lucher. Includes bibliographical references (leaves 103-114) and abstract. Also available in print.
3
Garefalaki, Anna. "Identification of regulatory regions that determine expression of murine CD8 locus". Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250198.
Testo completo
4
Robinson, Jonathan Matthew. "Identification of tumour-specific T-cells in colorectal cancer patients". Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485913.
Testo completoAbstract (sommario):
The ability to induce an immune response to a tumour is an attractive approach to cancer treatment, particularly when used in combination with surgery and chemotherapy or radiotherapy. In theory the use of such immunological techniques should be possible to help treat colorec~ cancer. Immunotherapy has shown encouraging results in the treatment of other cancers, namely malignant melanoma and renal cell c¥cinoma: The ability of these techniques to aid the treatment of advanced colorectal cancer has so far proved disappointing, although some encouragement has been observed. It has recently become possible to identify CD8+ T-cells specific for particular antigens using MHC class I tetramer staining. Carcinoembryonic antigen (CEA) is one such tumo~ antigen that is normally only expressed during embryonic development and not by adult tissues. However, in patients with colorectal cancer, CEA is over expressed and is therefore considered to be a tumour-specific antigen (TAA). T-cells specific for an epitope of CEA (CAP-I) can be identified using CAP-I loaded MHC class I tetramer molecules. The aim of this project was to assess the number and frequency of CEA specific CD8+ T-cells in colorectal cancer patients using this tetramer staining'protocol; in particular during the different treatments they receive prior to surgery, namely radiotherapy and ' chemotherapy. Previous methods to study these 'cells required large volumes of blood not suitable for patient studies. A novel and enhanced technique for the generation of antigen specific T-cells was employed which only required small volumes of blood . ideal for repeated patient testing. Cells recovered from the peripheral blood of healthy controls were cultured and observed for the proliferation of CAP-I specific T-cells, which were detected by tetramer staining, replicating the results of previous studies.
5
Hansson, Johan. "Activation and differentiation of cytotoxic T lymphocytes identification of district CTL subsets in the rat /". Lund : Dept. of Tumor Immunology, the Wallenberg Laboratory, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39158589.html.
Testo completo
6
Lam, Eric M. "IDENTIFICATION OF CYCLIN-DEPENDENT KINASE 5 IN T CELLS AND ITS ROLE IN REGULATING T CELL FUNCTION AND DIFFERENTIATION". Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1422014852.
Testo completo
7
Ulaganathan, Vijay Kumar. "Gene Expression Profiling of Encephalitogenic CD4+ T cells: Identification of Genes Controlling Migration of Effector T cells into the CNS". Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-122549.
Testo completo
8
Bosco, Anthony. "Identification of novel genes associated with allergen-driven T cell activation in human atopics /". Connect to this title, 2006. http://theses.library.uwa.edu.au/adt-WU2007.0023.
Testo completo
9
Pandey, Shubham. "Identification of Interleukin 4 - CXCL12 supportive loop in follicular lymphoma". Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1B031/document.
Testo completoAbstract (sommario):
Le lymphome folliculaire (FL) est le lymphome B indolent le plus fréquent. Outre des altérations géniques récurrentes, le micro-environnement tumoral, et notamment les cellules stromales lymphoides,joue un rôle majeur dans le développement de ce cancer. Cependant, la caractérisation in-situ des cellules stromales lymphoïdes chez l'homme tout comme les facteurs menant à la polarisation du stroma en un stroma protumoral ont été peu étudiés. Dans cette thèse, nous avons montré, que les cellules stromales présentes dans les ganglions et la moelle osseuse envahis des patients atteints de FL surexpriment fortement la chimiokine CXCL12. Nous avons ensuite tenté de comprendre les mécanismes responsables de cette induction. Alors que les cellules B tumorales induisent une surexpression de la chimiokine CCL2 dans les cellules stromales de façon dépendante de leur synthèse de TNF, elles ne contribuent pas à l'induction de CXCL12. A l'inverse, le principal compartiment TCD4 impliqué dans la croissance tumorale du FL, les cellules T follicular helper (TFH), augmentent l'expression de CXCL12 dans les cellules stromales. Le taux d'IL-4, la principale cytokine produite par les TFH de FL, est d'ailleurs corrélé à celui de CXCL12 au sein de ma niche tumorale du FL. De plus, à l’aide d'un modèle de différenciation en stroma lymphoide, nous avons démontré que l’IL4 induit l’expression de CXCL12 par les cellules stromale in vitro. Cette production est augmentée quand les cellules stromales sont déjà engagées vers la voie de différentiation lymphoide par un traitement TNF/LT qui favorise l'activation de STAT6 par l'IL-4. Nous avons validé ces résultats dans un modèle de formation d'organe lymphoide ectopique chez la souris. Enfin, CXCL12 induit la migration et l'adhésion au stroma des B de FL via l'activation de cascades de signalisations qui peuvent être abrogées par l'utilisation d'un inhibiteur de Btk utilisé en clinique, l'Ibrutinib. Ces résultats sont en faveur de l'intérêt de considérer la boucle IL-4/CXCL12 pour développer de nouvelles stratégies thérapeutiques dans cette pathologie constamment fataleFollicular lymphoma (FL) is the most frequent indolent B-cell lymphoma. Beside recurrent genetic alterations, tumor microenvironment, including lymphoid stromal cells, has been shown to play a key role in FL development. However, in situ characterization of lymphoid stromal cells is still lacking in humans and there are very few studies focusing on the factors that could lead to stroma polarization in normal and pathological context. In this thesis, we showed first that in FL, lymph node (LN) and bone marrow (BM) infiltrating stromal cells highly express the chemokine CXCL12. We next focused on the mechanisms underlying this upregulation. Interestingly, whereas malignant FL B cells induced overexpression of CCL2 in stromal cells in a TNF-dependent manner, they did not contribute to CXCL12 induction. Conversely, FL-infiltrating follicular helper T cells (FL-TFH), the key FL-supportive T-cell subset could trigger CXCL12 expression in stromal cells. IL-4 is the main FL-TFH-derived cytokine and showed a positive correlation with CXCL12 expression inside FL cell niches. Moreover, based on our in vitro lymphoid stroma differentiation model, we demonstrated that IL-4 promoted CXCL12 expression in stromal cells, together with a phenotype close to that identified in situ within FL cell niche. Such IL4 dependent CXCL12 regulation is more pronounced in stromal cells already committed towards lymphoid stromal cells by a prestimulation by TNF/LT in association with an increased STAT6 activation. These data were validated in a model of ectopic lymphoid organ formation in mice. Finally, CXCL12 induced FL B-cell migration, and adhesion to stromal cells through the activation of a signaling pathway that could be abrogated by the Btk inhibitor Ibrutinib. These data argue for considering IL-4/CXCL12 axis as a potential therapeutic target to disrupt FL protective cell niche in this still fatal malignancy
10
Bosco, Anthony. "Identification of novel genes associated with allergen-driven T cell activation in human atopics". University of Western Australia. School of Paediatrics and Child Health, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0023.
Testo completoAbstract (sommario):
[ Truncated abstract ] Atopic diseases such as asthma are thought to be driven to a significant extent by T helper memory cells which are programmed to respond in a harmful way to environmental allergens (e.g. house dust mite). Previous studies in humans and in animal models have established that activation of TH2 cytokine genes in T memory responses to allergens is central to the disease process. However, only a subset of atopics harbouring a TH2-memory response phenotype manifests clinical symptoms of disease. Moreover, clinical trials with TH2 antagonists in atopic patients have proven disappointing, suggesting underlying complexities in disease pathogenesis which escape regulation via these approaches. It was thus hypothesised that additional genes involved in the activation program of allergen-specific T memory cells which are central to disease pathogenesis remain unidentified. The aim of the current study was to identify such novel genes by applying microarray technology to survey genome-wide expression patterns in an in vitro model of allergen-driven human T cell activation. In contrast to previous human microarray studies in this area focusing on mitogen activated T cell lines and clones, the current study avoided the use of strong activation stimuli which have the potential to distort patterns of gene expression, and reports for the first time the findings of microarray analysis of house dust mite allergen-driven acute gene activation in recirculating T memory cells harvested from the peripheral blood of human atopics. ... Finally, methodology was established to investigate the function of the novel atopy-associated genes. In loss-of-function experiments, expression of DACT1 and CAMK2D was silenced in primary T cell responses driven by bacterial superantigens, a model system for studying T cell responses under conditions which mimic antigen-specific activation. Whilst silencing DACT1 and CAMK2D expression did not influence classical readouts of T cell function including proliferation and cytokine production, microarray profiling was employed to identify putative downstream transcriptional targets of each gene. The experimental strategy and optimised methodology presented herein can now be employed to investigate the molecular circuitry linking the novel atopy-associated genes to the T cell activation process. In conclusion, several novel genes associated with allergen-driven T memory responses in atopics have been first described in this thesis and represent logical candidates for more detailed immunological and genetic studies related to the pathogenesis of atopic diseases.
11
Zacharakis, Nikolaos. "Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells". Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/249827.
Testo completoAbstract (sommario):
Microbiology and ImmunologyPh.D.
Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. Immune system dysregulation, excessive deposition of collagen and microvascular damage in the skin and multiple internal organs are the main pathologic characteristics of the disease. Little is known about the mechanisms that are responsible for the pathogenesis of SSc. However, evidence has been accumulated demonstrating that T cells play a key role in the initiation and propagation of the disease. Previous studies in our laboratory have identified the presence of high proportions of identical β–chains TCR transcripts, demonstrating the presence of clonal expansion of T cells in skin biopsies from patients with SSc of recent onset. These T cells have undergone proliferation and clonal expansion in response to as yet unidentified antigen(s). The hypothesis that has been tested in this study is whether clonally expanded T cells in skin biopsies of patients with SSc of recent onset recognize self or non–self (possibly viral) putative SSc antigens, including DNA topoisomerase I, cytomegalovirus (CMV) and parvovirus. With the objective to identify the antigens recognized by clonally expanded T cells in skin biopsies of patients with SSc, we examined the presence of α– and β–chain TCR transcripts. Amplification of α–chain TCR transcripts by the non–palindromic adaptor PCR (NPA–PCR)/Vα specific PCR followed by cloning and sequencing revealed the presence of several clonally expanded α–chain TCR transcripts in skin biopsies from four patients with SSc and peripheral blood from one of these patients. Additionally, several clonally expanded β–chain TCR transcripts were identified in skin biopsies from all three of these patients with SSc examined, after NPA–PCR/Vβ specific amplification followed by cloning and sequencing. To identify the antigens recognized by these in vivo clonally expanded α– and β–chain TCR clones, full length α– and β– chain TCR transcripts containing the identified CDR3 regions from the clonally expanded TCR clones from the patients SSc–21 and SSc–22 were constructed. Pairs of clonally expanded, full length α– and β–chain TCR transcripts and appropriate controls were expressed in mutant TCR negative cells of the Jurkat T cell line (J.RT3–T3.5) by using a retroviral gene transfer and expression system. Each clonally expanded α–chain TCR transcript was combined with each clonally expanded β–chain TCR transcript from the same patient, generating T cells lines containing all pairing combinations of the clonally expanded TCR transcripts for each SSc patient. A total of 52 T cell lines were generated, including 10 control T cell lines. The surface expression of the TCR complex on these T cell lines was verified by flow cytometric analysis using antibodies against the α/β TCR and CD3epsilon. We employed an intracellular calcium mobilization assay to examine whether the Jurkat T cell lines transduced with the clonally expanded TCR transcripts from skin biopsies from patients with SSc (SSc–21 and SSc–22) recognize putative SSc antigens or their peptides presented by autologous EBV–transformed B cell lines. The putative SSc antigens that were tested are the self–antigen, DNA topoisomerase I and the viral antigens, cytomegalovirus and parvovirus which have been previously suggested to be involved in the pathogenesis of SSc. Significant intracellular calcium mobilization was observed in response to 3 DNA topoisomerase I and 2 CMV peptides by 5 T cell lines transduced with clonally expanded α– and β–chain TCR transcripts from patients SSc–21 and SSc–22.
Temple University--Theses
12
Thillai, Muhunthan. "Identification of antigen-specific T-cells and protein biomarkers for diagnosis of sarcoidosis". Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9541.
Testo completoAbstract (sommario):
Sarcoidosis is a multisystem granulomatous disease in humans with unknown aetiology and no current definitive diagnostic method. Intradermal inoculation of Kveim reagent (sarcoidosis tissue) was historically used for diagnosis, by causing a granuloma at injection site within 4-6 weeks, with high sensitivity and specificity. The immune mechanisms of this are poorly understood and the antigenic targets of granuloma-associated CD4+ T-cells are unknown. This T-cell infiltrate is oligoclonal, implicating a small number of antigenic targets. Previous work has shown that these are likely proteins. Aim 1 of this project involved identification of candidate protein antigens within Kveim reagent using proteomics, an established technology for the in depth quantitative differential analysis of complex protein mixtures. These sarcoidosis-specific proteins were analysed using gel electrophoresis with subsequent mass spectrometry and protein database interrogation. More than 80 proteins were identified as appearing specific to Kveim reagent or of significantly different abundance in sarcoidosis tissue compared to controls. These previously unreported proteins represent novel information that may help in the further understanding of the cellular pathways involved in disease. Additionally, multiplex cytokine analysis was performed on supernatant from sarcoidosis peripheral blood mononuclear cells incubated with both Kveim reagent and Kveim protein fractions to identify a secreted Th1 signal specific to disease. Information from the proteomics approach combined with this cytokine signal may be beneficial in creating an ex vivo immune based assay for diagnosis. Aim 2 of this project involved the direct analysis of serum and bronchoalveolar lavage (BAL) fluid by multiplex cytokine analysis to investigate signals which could serve as diagnostic biomarkers for the disease. BAL patterns in sarcoidosis were found indistinguishable from tuberculosis but significantly different to healthy volunteers. Significant differences were also found between sarcoidosis and tuberculosis serum, allowing for the creation of a model to reliably distinguish between the two diseases.
13
Schiering, Chris. "Identification of the cellular and molecular mechanisms of IL-23 driven intestinal inflammation". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:b33533f6-c7e1-4c77-9fd2-a3b174fb9bde.
Testo completoAbstract (sommario):
IL-23 is an essential mediator of chronic intestinal inflammation in experimental models of colitis. Polymorphisms in the IL23R locus are associated with IBD susceptibility in humans. The biological activity of IL-23 has been linked to Th17 cells but little is known about the cellular and molecular mechanism by which IL-23 drives intestinal inflammation. The work presented herein has identified that direct IL-23 signalling into CD4+ T cells was not only required for the accumulation of Th17 cells in the intestine but also modulated their phenotype. Through direct cell intrinsic effects on T cells, IL-23 drove the emergence of an IL-17A+IFN-γ+ population of T cells that co-expressed RORγ and T-bet. Interestingly, we found that expression of RORγ but not T-bet by T cells was required for the development of intestinal inflammation. Furthermore, colitis induced by T-bet deficient T cells was dependent on IL-17A, and showed a unique inflammatory phenotype, thus demonstrating that pathogenic intestinal Th17 responses can develop independently of T-bet. In addition, using transcriptional profiling we identified a core set of genes that is regulated by direct cell-intrinsic IL-23 signals into intestinal CD4+ T cells. This revealed a previously unrecognised role for IL-23 in suppressing Th2 associated genes, such as GATA3 and IL-33R. Functional experiments demonstrated that expression of GATA3 in CD4+ T cells limited their colitogenic potential, suggesting that IL-23-mediated inhibition of GATA3 might contribute to the development of intestinal inflammation. Finally, we described a novel function for IL-33 as a factor that promotes Foxp3+ iTreg differentiation in vitro and in vivo through direct effects on T cells. This activity of IL-33 was inhibited in the presence of IL-23, providing a mechanistic link for the known role of IL-23 in restraining iTreg generation. Collectively, these data suggest that IL-23 promotes acquisition of a pathogenic effector T cell phenotype through multiple mechanisms. This indicates that therapeutic blockade of IL-23 is likely to reduce pro-inflammatory mediators while also facilitating the expansion of regulatory pathways that might help to re-establish intestinal homeostasis.
14
Yeh, Ming-Hsin. "Identification of CD8+ T cell-stimulating shared antigens that are uncovered in CT26 vaccinated mice in the absence of CD25+ regulatory T cells". Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431953.
Testo completo
15
Hancock, Gemma. "Identification of immunological targets for HIV-1 vaccine and cure strategies". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:de163905-a755-43f1-b0c3-fdd737a2cf5b.
Testo completoAbstract (sommario):
HIV-1 chronically infected individuals represent a large disease burden, making the development of a therapeutic vaccine for use in chronic infection a priority. However, therapeutic vaccination has not been successful to date. Most approaches have employed viral vectored vaccines encoding full length viral proteins, which aimed to boost pre-existing CD8+ T cell responses by mimicking natural HIV-1 infection. Simply boosting these pre-existing CD8+ T cell responses which have previously failed to control the virus may be insufficient. Although HIV-1 has a huge capacity to diversify, certain regions are less tolerant of mutations due to structural and functional constraints. We therefore hypothesised that it would be necessary to redirect the immune response to more vulnerable regions of the proteome, such as conserved regions. HIVconsv is a rationally designed conserved region vaccine. Vaccination of 19 chronically HIV-1 infected HAART treated patients with MVA.HIVconsv was safe and well tolerated. There was a significant increase in the magnitude of HIVconsv-specific T cell response following vaccination (p = 0.001), as measured by IFN-γ Elispot assay, but changes observed in vaccinees did not reach statistical significance when compared with placebo recipients (p = 0.48). The capacity of CD8+ T cells to inhibit HIV-1 replication in vitro is highly predictive of virus control in vivo and is thus a possible surrogate of vaccine efficacy. There was a trend towards increased CD8+ T cell mediated inhibition following vaccination with 2x108pfu MVA.HIVconsv (17% inhibition pre- vs 54% inhibition post-vaccination, p = 0.06). However, measurement of the latent HIV-1 reservoir by quantification of total HIV-1 DNA in circulating CD4+ T cells by droplet digital PCR showed no reduction in size upon vaccination, indicating CD8+ T cells induced by vaccination with MVA.HIVconsv were not of sufficient potency to impact the reservoir. In a second cohort of HIV-1 infected individuals, antiviral inhibitory activity was measured in 36 HIV-1-infected STEP and Phambili trial participants. Sustained potent CD8+ T cell antiviral inhibitory responses were rare but were strongly correlated with IFN-γ responses to so-called ‘beneficial’ low entropy regions in HIV-1 Gag and Pol, that had been reported previously to be associated with HIV-1 control, (r = 0.69, p = 0.0001). This correlation was still significant after controlling for protective HLA alleles, whereas responses to conserved elements were only weakly correlated with viral inhibition (r = 0.41, p = 0.04). These data indicate that immunogens that are based on the selection of regions within the viral proteome by conservation score alone may not induce the most effective HIV-1-specific T cell responses and they highlight the importance of systematically selecting specific regions associated with HIV-1 control, together with exclusion of immunodominant decoy epitopes.
16
Derry, David Douglas. "Identification of anti-microbial and anti-viral proteins expressed by cytotoxic CD8+ T cells". Thesis, St George's, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407492.
Testo completo
17
Cao, Tingting, e 曹婷婷. "Identification and evaluation of protective activity of a T cell epitope targeting nucleoprotein of H5N1 influenza virus". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47323218.
Testo completoAbstract (sommario):
The outbreaks of human influenza caused by highly pathogenic avian influenza
H5N1 virus have attracted a lot of attention and public concern. Effective and
universal vaccines may be the best means for prevention and control of the influenza.
Taking into account that viral clearance and recovery from influenza A virus infection
have been demonstrated to be correlated to specific cytoxic T lymphocyte (CTL)
instead of neutralizing antibodies, it is important to develop effective vaccines which
are capable of inducing not only neutralizing antibody but also CTL responses.
Furthermore, T cell epitopes are usually more conserved than neutralizing epitopes.
However, rare information concerning human T cell epitopes specific to H5N1 virus
has been reported so far.
This study was designed to test our hypothesis that novel and potent human CTL and
Th epitopes specific to NP protein of H5N1 virus may be identified in vaccinated
and/or infected HLA-A2/DR1 transgenic mice (SURE/L1), while protective epitopes
may be further defined from the identified T cell epitopes in the mice challenged with
lethal dose of the virus. We used SURE/L1 mouse model because it contains HLA-A2
(*0201) and -DR1 (*0701), both are the second highest frequency of HLA class I and
II in Chinese. Since the NP gene is relatively conserved among different clades or
strains of H5N1 virus, we selected viral protein NP as the target. Furthermore, we
screened the T cell epitopes in splenocytes not only from vaccinated mice but also
from survived mice infected with gradually increased dose of H5N1 virus, because
the T cell epitopes identified in both vaccinated and infected mice or in infected mice
alone might have higher potential to be protective epitopes.
In this study, a novel HLA-DR1 (class II) restricted T cell epitope NP368-382, NPII-7,
was identified in both vaccinated and infected mice. Two doses of NPII-7 peptide
boosting in the mice induced very strong Th1 and CTL responses but no NP specific
antibody responses. The vaccination of additional 2 doses of NPII-7 also provided
partial protection against lethal challenge of H5N1 virus in the mice, whereas NP
DNA vaccination alone did not show any protective effect. The protective effect may
be attributed to the strong Th1 and CTL responses induced by the NPII-7 vaccination,
because both NP DNA and NPII-7 vaccinations could not induce neutralizing
antibody response.
Notably, a HLA class II restricted peptide, NPII-7, may induce not only Th1
responses but also more strong HLA class I restricted T cell (CTL) responses. It may
probably due to that the HLA-DR1 restricted T cell epitope
(NENMEAMDSNTLELR) contained the full sequence of a reported HLA-A2
restricted CTL epitope (AMDSNTLEL), named NP-17 in this study. Although it
needs to be further defined whether this novel epitope is really a HLA-DR1 restricted
T cell epitope, or it shares the activity of HLA-A2 restricted T cell epitope, or it is
just an alternate HLA-A2 restricted T cell epitope, this study has identified a novel T
cell epitope and proved that it is a protective T cell epitope.published_or_final_version
Microbiology
Master
Master of Philosophy
18
Kawahara, Masahiro. "Identification of HLA class 1-restricted tumor-associated antigens in adult T cell leukemia cells by mass spectrometric analysis". Kyoto University, 2007. http://hdl.handle.net/2433/135730.
Testo completo
19
Chau, Suk-yi, e 周淑怡. "A study of the expression of Sonic hedgehog and its receptors in T cells and the identification of Sonic hedgehog dowm-stream targets inactivated CD4+T cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31386234.
Testo completo
20
Chau, Suk-yi. "A study of the expression of Sonic hedgehog and its receptors in T cells and the identification of Sonic hedgehog dowm-stream targets in activated CD4+T cells". Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B31386234.
Testo completo
21
Kleemann, Patrick [Verfasser]. "Mass spectrometric identification of Varicella-Zoster Virus (VZV) proteins recognized by human T cells / Patrick Kleemann". Mainz : Universitätsbibliothek Mainz, 2012. http://d-nb.info/1019669047/34.
Testo completo
22
Fogg, Mark. "Identification of bovine respiratory syncytial virus proteins and epitopes recognised by bovine CD4⺠T cells". Thesis, University of Reading, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270223.
Testo completo
23
Rani, Aradhana. "Identification and analysis of Il-2 induced Stat5 Target genes in Human CD4 and CD8 T cells". Thesis, King's College London (University of London), 2010. https://kclpure.kcl.ac.uk/portal/en/theses/identification-and-analysis-of-il2-induced-stat5-target-genes-in-human-cd4-and-cd8-t-cells(efe24c7c-eb52-44f8-8e58-86b6ca0dfdfa).html.
Testo completoAbstract (sommario):
Signal transducers and activators of transcription (STAT) 5a and 5b, are key signalling proteins activated by the cytokine interleukin-2 (IL-2), and therefore critically regulates important immunological processes such as T cell homeostasis and immune-regulation. While the biological functions of STAT5 are well established from murine genetic studies, the downstream mediators of these proteins are poorly understood. In this study, an improved chromatin immunoprecipitation (ChIP)-cloning method, using magnetic microbeads for immunocapture of chromatin was developed to identify in-vivo STAT5a and STAT5b binding sites in fresh and activated primary human CD4 and CD8 peripheral T cells. Six libraries were generated, which identified 329 STAT5a and/or STAT5b-specific binding sites of which 87% contained canonical GAS motifs, TTCN3GAA and/or TTN5AA. Genomic mapping of sites revealed the striking observation that the majority of STAT5-binding sites identified here mapped to intergenic (>50kb upstream) or intronic, rather than promoter proximal regions. Bioinformatic analyses, using Gene Ontology programmes to annotate and functionally classify the genes associated with binding sites, predicted novel functions for STAT5 such as transport and metabolism, in addition to previously known functions such as cell differentiation, proliferation, signal transduction, apoptosis and development. Additionally, several target-genes were identified, whose aberrant functions are associated with malignant transformation of cells, consistent with the frequent dysregulation of STAT5 noted in various cancers. ChIP-PCR validation studies on a subset of sites from each library, demonstrated that 98% were bonafide STAT5 binding sites. Kinetic gene expression analyses performed on 31 annotated genes, by qRT-PCR revealed 17 novel target-genes that were upregulated (76%) or downregulated (24%) following IL-2 stimulation, and included two lineage-specification factors, c-MAF and RORA. Given the importance of IL-2 in facilitating CD4 Th2 cell differentiation, the regulation of c-MAF by STAT5 was functionally characterised further using biochemical and molecular techniques. These studies revealed that the epigenetic regulation of c-MAF is dependent on STAT5 and IL-2 signalling. In conclusion, this study has identified a number of novel STAT5 regulated genes downstream of IL-2 activation of T cells, and provides an insight into the various cellular functions regulated by these proteins.
24
Cohen, Shannon. "Identification et caractérisation fonctionnelle de sous-populations monocytaires circulantes chez l'homme". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC241.
Testo completoAbstract (sommario):
Les monocytes sont des leucocytes circulants, précurseurs de cellules dendritiques et de macrophages, dont le phénotype est hétérogène. L’association entre les sous-populations de monocytes humains décrites dans la littérature et les fonctions dans la réponse immunitaire reste difficile. Les différentes populations de monocytes humains sont classées en fonction de l’expression de molécules de surface CD14 et CD16. Trois populations ont ainsi été identifiées : les monocytes classiques CD14+ CD16neg, les monocytes non-classiques CD14dim CD16+ et les monocytes intermédiaires CD14+ CD16+. Les fonctions attribuées à ces populations sont diverses et enchevêtrées. En particulier, les propriétés pro- et anti-inflammatoires associées à ces populations de cellules sont redondantes et conflictuelles suivant les auteurs. En situation inflammatoire, l’augmentation de la fraction de monocytes CD16+ suggère leur implication dans le développement et/ou dans l’amplification de l’inflammation. L’objectif de cette thèse porte sur une meilleure définition des populations monocytaires afin de pouvoir les subdiviser en sous-populations dont les fonctions seraient mieux définies. Ce travail s’est inscrit dans un projet à long terme du laboratoire visant à l’analyse phénotypique aussi exhaustive que possible des monocytes, utilisant les outils d’analyses biologiques et informatiques actuels. Cela a permis de mettre en évidence l’existence d’une population de monocytes de plus grande taille. Ces « large » monocytes se subdivisent en populations CD16neg et CD16+ (respectivement nommées la14+16neg et la14+16+). Les monocytes communément analysés, de taille plus petite ou « small », se subdivisent comme attendu en trois sous-populations identifiées ici comme monocytes sm14+16neg largement majoritaire, sm14dim16+ et sm14+16+....Enfin, l’analyse des phénotypes de monocytes circulants en situation pathologique a été effectuée chez des grands brûlés. Ces patients ont une susceptibilité accrue à l’infection due, entre autres, à des réponses immunitaires innées déficientes. Les résultats obtenus chez 18 patients prélevés à l’admission et à 7 et 28 jours plus tard permettent d’identifier différents profils de modifications phénotypiques des monocytes et leur évolution en fonction de l’état clinique. Cette étude a également permis de mettre en évidence l’existence d’une population de cellules à forte granulosité, amplifiée de façon importante chez les patients et dont les fonctions sont en cours d’analyseMonocytes are circulating leucocytes, precursors of dendritic cells and macrophages, whose phenotype is heterogeneous. The association between human monocyte subsets described in the literature and the functions in the immune response remains difficult.The different populations of human monocytes are classified according to the expression of surface markers CD14 and CD16. Three populations have thus been identified: the classical monocytes CD14+ CD16neg, the non-classical monocytes CD14dim CD16+ and the intermediate monocytes CD14+ CD16+. The functions assigned to these populations are diverse and entangled. In particular, the pro- and anti-inflammatory properties associated with these populations are redundant and conflicting depending on the authors. In an inflammatory situation, the increase of the CD16+ monocyte fraction suggests their involvement in the development and/or the amplification of inflammation.The aim of this thesis is to improve the definition of monocytes populations so that they can be subdivided into subpopulations whose functions are better defined. This work was part of a long term laboratory project which has the goal to the most comprehensive phenotypic analysis of monocytes, using current biological and computer analysis tools. This highlighted to demonstrate the existence of a larger monocyte population. These "large" monocytes are subdivided into CD16neg and CD16+ populations (respectively named la14+16neg and la14+16+). Monocytes commonly analyzed, of smaller size or "small", are subdivided as expected in three subpopulations identified here as monocytes sm14+16neg largely in the majority, sm14dim16+ and sm14+16+.Finally, the analysis of the phenotypes of circulating monocytes in pathological situation was conducted in burn victims. These patients have an increased susceptibility to infection due, among other things, to deficient innate immune responses. These results obtained in 18 patients taken at admission and at 7 and 28 days later permitted to identify different phenotypic modification profiles of monocytes and their evolution depending on the clinical state. This study has also highlighted the existence of a population of cells with high granulosity, greatly amplified in patients and whose functions are being analyzed
25
Debuisson, Delphine. "Rétrocontrôle des réponses Th2 par l'interleukine-6 et identification d'un nouveau facteur de transcription exprimé par les lymphocytes T helper folliculaires". Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209158.
Testo completoAbstract (sommario):
L’objectif de notre travail a été de caractériser le rôle de l’IL-6 dans la différenciation des lymphocytes Tfh et des lymphocytes Th2. Les lymphocytes Tfh ont pour fonction d’aider les lymphocytes B à produire des anticorps indispensables pour nous protéger contre divers pathogènes. Les lymphocytes Th2, quant à eux, sont spécialisés dans l’élimination de parasites extracellulaires tels que les helminthes.Dans un premier temps, nous avons voulu identifier les gènes dont l’expression est induite par l’IL-6, avec comme objectif une meilleure compréhension des mécanismes permettant aux lymphocytes T de se différencier en cellules Tfh.
Au cours de notre travail, nous avons identifié le facteur de transcription, MyoR (Myogenic Repressor) comme étant exprimé au sein des lymphocytes T helper et dont l’expression est induite par l’IL-6. Nos observations expérimentales ont démontré que le facteur MyoR n’est pas indispensable pour la différenciation des lymphocytes Tfh, ni pour leur fonction. Cependant, l’expression de l’ARNm codant pour MyoR pourrait être utilisée comme un biomarqueur des cellules Tfh in vitro ou in vivo.
Nous avons ensuite caractérisé la réponse immune induite in vivo par des cellules présentatrices d’antigènes issues de souris déficientes pour l’IL-6. Cette approche nous a permis de mettre en évidence le rôle immunosuppresseur de l’IL-6 sur le développement des réponses de type Th2. En effet, nous avons montré que l’injection de BMDCs (Bone Marrow derived dendritic cells) IL-6-/- dans des souris receveuses de type sauvage induisent une réponse Th2 augmentée in vivo.
Nos résultats suggèrent que l’inhibition de la réponse Th2 par l’IL-6 in vivo et in vitro pourrait impliquer la présence d’un ou de plusieurs miRNAs.
Cette inhibition pourrait être un mécanisme de rétrocontrôle afin d’éviter une exacerbation de la réponse immune Th2.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
26
Han, Rui [Verfasser]. "Identification of triptolide as a potential aryl hydrocarbon receptor antagonist in human T cells and keratinocytes / Rui Han". Kiel : Universitätsbibliothek Kiel, 2011. http://d-nb.info/1020245166/34.
Testo completo
27
Nhim, Cathy. "Identification de lymphocytes T spécifiques des médicaments chez des individus non allergiques". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00769921.
Testo completoAbstract (sommario):
Chez des patients allergiques, il est possible de retrouver dans leur sérum desanticorps spécifiques du médicament (IgE) et dans leur sang des lymphocytes T spécifiquesdu médicament. La présence de LT spécifiques du médicament chez des patients allergiquessuggère la présentation du médicament par des cellules présentatrices d'antigène telles queles cellules dendritiques.Nous nous sommes alors intéressés à mieux comprendre l'implication deslymphocytes T et des cellules dendritiques dans le développement des allergies auxantibiotiques comme la pénicilline G (ou Benzyl-Pénicilline) ou le sulfaméthoxazole.Ce travail de thèse a permis: i) de démontrer la présence de lymphocytes Tspécifiques de la pénicilline G dans le sang périphérique de donneurs non allergiques à unefréquence mesurable, ii) de développer deux approches expérimentales et de modélisationpour l'identification des épitopes potentiellement présentés aux lymphocytes T et iii)d'étudier l'effet des médicaments sur les cellules dendritiques.Les perspectives de ce travail sont de mieux comprendre les mécanismes impliquésdans les allergies médicamenteuses au niveau des lymphocytes T et des cellules dendritiqueset de développer des tests de prédiction du " potentiel allergique " des médicaments, afinde mieux prédire les allergies médicamenteuses lors du développement des médicaments.
28
Rainer, Roman Josef. "Identification of differential regulation in central carbon metabolism between related cell lines". Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/22117.
Testo completoAbstract (sommario):
Darmkrebszellen und T-Zellen regulieren ihren zentralen Kohlenstoffmetabolismus um
ihren anabolen Bedarf zu erfüllen. Tumorzellen mit einer KRAS- oder BRAF-Mutation
zeigen ein schnelles Wachstum, welches eine Umprogrammierung des Metabolismus vor
aussetzt. Der mitochondriale T-Zellen-Aktivierungsinhibitor (TCAIM) ist bekannt dafür
die mitochondriale Zellstruktur zu beeinflussen. Der Einfluss auf den Metabolismus nicht
klar.
In dieser Arbeit präsentiere ich erstmalig ein mathematische Model des zentralen Kohlen
stoffmetabolismus in Darmkrebszellen und T-Zellen. Mithilfe dieses Modells analysiere
ich, wie sich die Regulation in ähnlichen Zelllinien unterscheidet. In Bezug auf die Darm
krebszellen vergleiche ich BRAF-(CaCO2-BRAFV600E), KRAS-(CaCO2-KRASG12V) mu
tierte Zelllinien mit einer Basiszelllinie (CaCO2-control) und zeige, dass der Kohlenstoff
metabolismus in BRAF-mutierten Zellen im Vergleich zu den beiden übrigen Zelllinien
herabreguliert ist. Das Modell bestätigt außerdem, dass der Monocarboxylattransporter
(MCT) in den Darmkrebszellen eine wichtige Rolle, insbesondere in den KRAS mu
tierten Zellen, spielt. In T-Zellen zeigt der Vergleich von Wildtypzellen (CD8 T-Zellen)
mit TCAIM homozygoten Zellen (TCAIM homozygote CD8 T-Zellen), dass der Kohlen
stoffmetabolismus in zweiteren überwiegend herabreguliert und weniger aktiv ist. Diesen
Effekt konnte ich durch die Analyse von RNASeq-Daten der jeweiligen Zelltypen bestä-
tigen. Des Weiteren stelle ich fest, dass sich der Tricarbonsäurezyklus umkehrt, wenn
durch die Glykolyse nicht ausreichend Laktat exportiert und die Biomasseproduktion
unterstützt werden kann.
Meine Arbeit stellt damit insgesamt einen neuartigen Ansatz zur Integration von Meta
bolomik und RNAseq Daten dar, um die Regulation des zentralen Kohlenstoffmetabo
lismus zu verstehen.Colon cancer cells and T cells regulate central carbon metabolism to meet their anabolic needs. In KRAS and BRAF tumors, metabolic reprogramming is a premise to support rapid proliferation. In T cells, the mitochondrial T cell activation inhibitor (TCAIM) is known to affect mitochondrial morphology but its effect on cellular metabolism is not well understood. Via mathematical modelling, I investigate the differential regulation of closely related cell lines. I present the first mathematical model for colon cancer and T cell metabolism, unraveling differential regulation between related cell lines. The model shows that CaCO2-BRAFV600Ecells are mostly downregulated compared to CaCO2-KRASG12Vand CaCO2-control. Additionally, it demonstrates the critical role of monocarboxylate transporter (MCT), especially for CaCO2-KRASG12V. Concerning T cells, I compare wild-type T cells to homozygous TCAIM T cells. This unveils that TCAIM homozygous cells have a mostly downregulated TCA cycle, validated by RNASeq data, and are less metabolically active than wild-type T cells. Furthermore, if the glycolytic flux is not sufficient to support lactate export and biomass production, the model reveals that the TCA cycle is reversed as it requires less regulation. Taken together, this work presents a novel approach to integrate data referring to metabolic and genetic regulation of metabolism. On this basis, we can now better discriminate the metabolic capacity of CaCO2-control, CaCO2-BRAFV600E, CaCO2-KRASG12V, wildtype CD8 T cells, and homozygous TCAIM CD8 T cells.
29
Gérart, Stéphane. "Identification d’un nouveau mécanisme de contrôle de l’homéostasie des lymphocytes T iNKT et MAIT". Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05TO22/document.
Testo completoAbstract (sommario):
Les cellules Invariant Natural Killer T (iNKT) représentent une sous-population particulière de cellules T qui se distingue par son développement, ses fonctions et les ligands qu’elle reconnaît. Chez l’homme, les cellules iNKT expriment le réarrangement Vα24-Jα18/Vβ11 et reconnaissent des glycosphingolipides présentés par la molécule monomorphe du CMH de classe I CD1d. De plus, elles produisent rapidement de grandes quantités de cytokines, et sont ainsi considérées comme des cellules T ayant des caractéristiques innées. Les mécanismes moléculaires qui régulent l’homéostasie descellules iNKT ne sont pas complètement compris. La protéine XIAP (X-linked Inhibitor of Apoptosis) est un inhibiteur physiologique des caspases 3, 7 et 9. Des mutations du gène XIAP sont à l’origine du syndrome lymphoprolifératif lié à l’X de type 2 (XLP-2), un déficit immunitaire primitif (DIP) caractérisé par une susceptibilité accrue à l’infection par le virus Epstein Barr (EBV). Les patients souffrant du XLP-2 présentent une forte réduction de leur nombre de cellules iNKT dans le sang. Au cours de mon travail de thèse, j’ai montré que XIAP est requis pour la survie des cellules iNKT humaines. Cette fonction de XIAP corrèle avec un phénotype pro-apoptotique des cellules iNKT qui n’est pas retrouvé dans les cellules T conventionnelles. La susceptibilité accrue à l’apoptose des cellules iNKT est observée en utilisant des stimuli de la voie intrinsèque ou extrinsèque de l’apoptose. Les cellules iNKT, contrairement aux cellules T conventionnelles expriment des quantités élevées de protéines pro-apoptotiques comme les caspases 3 ou 7 ou Bid. Ce phénotype proapoptotique est acquis de manière précoce, puisqu’il est déjà présent dans des cellules iNKT de thymus ou de sang de cordon. L’extinction de XIAP dans des cellules iNKT et l’analyse de patients déficients en XIAP indiquent que XIAP est un inhibiteur efficace de l’apoptose dans les cellules iNKT alors qu’il n’a qu’un effet modéré dans les cellules T conventionnelles. J’ai ensuite montré que le phénotype pro-apoptotique des cellules iNKT est dépendant de l’expression du facteur de transcription PLZF. Celui-ci est déjà connu comme étant nécessaire à l’acquisition des fonctions effectrices de cescellules. De manière concordante, la surexpression de PLZF dans des cellules T conventionnelles conduit à un phénotype pro-apoptotique et à une augmentation de l’expression de la caspase 3. Récemment, une deuxième population de cellules T invariantes, les cellules MAIT (Mucosal Associated Invariant T) a été décrite. Ces cellules expriment un TCR semi-invariant Vα7.2-Jα33 et partagent avec les cellules iNKT certaines caractéristiques qui en font des cellules T innées comme les cellules iNKT. De la même manière que les cellules iNKT, les cellules MAIT ont un phénotype proapoptotiqueet sont diminuées dans le sang des patients déficients en XIAP. Ce phénotype proapoptotique est aussi dépendant de PLZF. De manière intéressante, un patient déficient en XIAP et ayant un nombre normal de cellules iNKT a été identifié. Ce patient n’a pas encore rencontré l’EBV, suggérant que la diminution des cellules iNKT chez les patients déficients en XIAP est due à une apoptose augmentée dans un contexte d’infection par l’EBV. Enfin, j’ai obtenu des données préliminaires suggérant que l’EBV utilise un mécanisme d’échappement aux cellules iNKT en diminuant l’expression de CD1d à la surface des cellules B. Mon travail de thèse a donc permis d’identifier une voie de régulation inconnue des lymphocytes T innés qui dépend de XIAP et de PLZF. PLZF est donc un facteur clé pour la différentiation et l’homéostasie des cellules T innées en régulant l’acquisition de leurs fonctions effectrices et en limitant leur survie. Ces observations ont aussi permis d’identifier le premier DIP associé à un déficit en cellules MAIT. Enfin, ces résultats suggèrent un rôle des cellules iNKT dans le contrôle de l’infection par l’EBVInvariant natural killer T (iNKT) lymphocytes represent a peculiar T cell-lineage that differs from conventional T cells by its development, function, and ligands it recognizes. In humans, iNKT cells express an invariant TCR made of the V?24-J?18/V?11 rearrangement, which recognizes glycosphingolipids presented by the MHC class I monomorphic molecule CD1d. Moreover, they rapidly produce high amounts of cytokines when stimulated and are thus considered as innate-like T cells. The molecular mechanisms that control the homeostasis of iNKT are poorly understood. XIAP (X-linked Inhibitor of Apoptosis) is a physiological inhibitor of caspases 3, 7 and 9 and is mutated in the X-linked lymphoproliferation syndrome 2 (XLP-2), a rare primary immunodeficiency (PID) characterized by a peculiar susceptibility to Epstein-Barr virus (EBV) infection. Patients with a XIAP deficiency exhibit a strong reduction of their iNKT cells in blood. Here, I report that XIAP is required for the survival of iNKT cells in humans. The requirement of XIAP correlates with a pro-apoptotic phenotype of iNKT cells that is not observed in conventional T cells. The increased susceptibility to apoptosis of iNKT cells was observed upon stimuli that trigger either extrinsic or intrinsic apoptosis pathways. iNKT cells by contrast to conventional T cells express elevated amounts of pro-apoptotic molecules including caspases 3 or 7 and Bid. The pro-apoptotic phenotype of iNKT cells is early acquired since iNKT cells from cord blood and thymus display a similar pro-apoptotic phenotype. Knock-down of XIAP in iNKT cells and analysis of XIAP-deficient humans indicate that XIAP is a potent inhibitor of apoptosis in iNKT cells while it has only a moderate effect in conventional T cells. I also show that this pro-apoptotic phenotype of iNKT cells is dependent of the expression of the transcription factor PLZF. This factor is already known to be necessary for the acquisition of the effector functions of these cells. Conversely, over expression of PLZF in conventional T cells leads to a pro-apoptotic phenotype and to an increased expression of caspase 3. Recently, a second invariant T cell subpopulation, the mucosal associated invariant T (MAIT) cells was identified both in humans and mice. These cells express a semi-invariant TCR made of V?7.2-J?33 rearrangements and share with iNKT cells a number of developmental, functional and phenotypical features that lead to consider MAIT cells as innate-like T cells like iNKT cells. Similarly, MAIT cells also exhibit a pro-apoptotic phenotype and are decreased in XIAP-deficient humans. The pro-apoptotic phenotype of MAIT cells is also dependent on PLZF. Interestingly, one XIAP-deficient patient with normal iNKT cell number was identified. This patient has not yet encountered EBV, suggesting that reduction of iNKT cells in XIAP-deficient patients is likely due to increased apoptosis in the context of EBV infection. I also show that EBV might have an escape mechanism from iNKT cells by down-regulating the expression of CD1d on the surface of B cells. My thesis works identify a previously unknown pathway controlling innate T cell homeostasis depending on XIAP and PLZF. PLZF is thus a key factor involved in the differentiation and the homeostasis of innate T cells by regulating the acquisition of their effector functions and their survival. I also identified the first PID associated with a defect in MAIT cells. Finally, these results provide evidences that iNKT cells might play a role against EBV infection
30
Brown, Jennifer L. "A molecular and immunological investigation of cellular responses to dengue virus identification of potentially upregulated host genes and the constructionof a vaccinia virus expressing the dengue 1 Hawaii NS3 protein". Link to electronic version, 2000. http://www.wpi.edu/Pubs/ETD/Available/etd-0330100-124248/.
Testo completo
31
Brown, Jennifer L. "A Molecular and Immunological Investigation of Cellular Responses to Dengue Virus: Identification of Potentially Upregulated Host Genes and the Construction of a Vaccinia Virus Expressing the Dengue 1 Hawaii NS3 Protein". Digital WPI, 2000. https://digitalcommons.wpi.edu/etd-theses/187.
Testo completoAbstract (sommario):
The purpose of this thesis for the degree of Master of Science was to use molecular and immunological techniques to study cellular responses to dengue virus infection. In the initial study, Differential Display was used to compare mRNA expression in dengue-infected K562 cells and mock-infected cells. Cloning and sequencing were then used to identify cellular genes that were potentially up-regulated in response to Dengue virus infection. These genes included bleomycin hydrolase and a dystrophin homologue. The goal of the later part of this research was to construct a recombinant vaccinia virus expressing the dengue 1 Hawaii NS3 protein. Cytotoxic T-lymphocyte assays and protein gel electrophoresis showed that the NS3 protein was being expressed. This construct was then used to study the cytotoxic T-cell response of a dengue 1 vaccine recipient. The results of this study showed that this individual has dengue 1 NS3 specific T-cells and also that this vaccinia virus can be used for subsequent T-cell studies.
32
Sardar, Harjinder Singh. "Molecular Interactions of Arabinogalactan-Proteins (AGPs) in Tobacco Bright Yellow-2 Cultured Cells and Functional Identification of Four Classical AGPs in Arabidopsis". Ohio University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1187112623.
Testo completo
33
Heinz, Gitta Anne Maren [Verfasser], e Daniel [Akademischer Betreuer] Krappmann. "Identification of Roquin-regulated mRNAs in T helper cells and molecular characterization of the Roquin-RNA interaction / Gitta Anne Maren Heinz. Betreuer: Daniel Krappmann". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1095484796/34.
Testo completo
34
Fichtner, Alina Suzann [Verfasser], e Thomas [Gutachter] Herrmann. "Alpaca, armadillo and cotton rat as new animal models for nonconventional T cells: Identification of cell populations and analysis of antigen receptors and ligands / Alina Suzann Fichtner ; Gutachter: Thomas Herrmann". Würzburg : Universität Würzburg, 2020. http://d-nb.info/1209059231/34.
Testo completo
35
Badran, Bassam. "Identification of the human CD3gama gene promoter, characterization of specific promoter elements and analysis of their activity in normal and HIV-infected CD4+T cells". Doctoral thesis, Universite Libre de Bruxelles, 2003. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211233.
Testo completo
36
Premachandran, Nair Anoop Chandran [Verfasser], Jörg [Gutachter] Wischhusen, Utz [Gutachter] Fischer e Gunter [Gutachter] Meister. "Identification and functional characterization of TGF-β inducible, immunosuppressive miRNAs in human CD8+ T cells / Anoop Chandran Premachandran Nair. Gutachter: Jörg Wischhusen ; Utz Fischer ; Gunter Meister". Würzburg : Universität Würzburg, 2015. http://d-nb.info/1108781322/34.
Testo completo
37
Huppert, Cécile. "Développement d’un modèle de coculture cellules dendritiques lymphocytes T pour l’évaluation du danger des substances sensibilisantes". Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0195/document.
Testo completoAbstract (sommario):
Les allergies représentent un problème majeur dans le domaine des maladies professionnelles et ont un impact sérieux sur la vie des travailleurs. Les allergies professionnelles sont principalement cutanées et respiratoires ; elles peuvent être causées par des produits chimiques de bas poids moléculaire. Dans le passé, les tests destinés à identifier les produits susceptibles d’entraîner des allergies étaient réalisés sur l’animal. Or, la législation européenne engage à limiter le recours à l’expérimentation animale pour évaluer le pouvoir sensibilisant des substances chimiques, incitant à développer des tests in vitro de substitution. C’est dans ce contexte que nous avons cherché à développer des modèles de cultures cellulaires destinés à identifier les substances sensibilisantes. Un premier modèle utilisant des cellules dendritiques dérivées de moelle osseuse (BMDC) de souris BALB/c a été développé et a donné des résultats prometteurs pour l’identification des produits sensibilisants et leur catégorisation selon leur puissance sensibilisante. De plus, la voie de signalisation Nrf2/Keap1 semble être impliquée dans la réponse de ce modèle cellulaire aux sensibilisants. Dans le but de compléter ce modèle et d’évaluer la capacité des BMDC à activer les lymphocytes T (LT), un modèle de coculture de BMDC et LT a été mis au point avec un sensibilisant de référence avant d’être testé sur un ensemble de produits de référence (sensibilisants cutanés et respiratoires, irritants et non sensibilisants). Les BMDC de notre modèle, exposées à des sensibilisants, se sont révélées capables d’activer les LT en coculture. Enfin, des essais préliminaires utilisant des cellules de souris de souche C57BL6/J dans notre modèle de coculture ont donné des résultats comparables à ceux obtenus avec des cellules issues de la souche BALB/c. Les modèles de cultures cellulaires BMDC et de coculture BMDC-LT sont prometteurs dans le cadre du développement de méthodes de substitution à l’expérimentation animale pour l’évaluation du pouvoir sensibilisant de substances chimiquesAllergies constitute an important issue in the field of occupational health and have a serious impact on the lives of workers. Occupational allergies are mainly contact and respiratory allergies and can be caused by low molecular weight chemicals. In the past, the tests that were used to identify the potential allergens were carried out on animals. However, European legislation has provided the impetus for reducing the use of animal testing to assess the sensitization potential of chemicals and promoted the development of alternative in vitro tests. In this context, we aimed to develop cell culture models to identify sensitizers. A first model using bone marrow derived dendritic cells (BMDC) from BALB/c mice was developed and showed promising results for identifying sensitizers and classify them according to their allergenic potency. Moreover, the Nrf2/Keap1 pathway seems to be involved in the response of this cell model to sensitizers. In order to supplement this model and to assess the functionality of BMDC, a BMDC-T cell (TC) coculture model was developed with a reference sensitizer before being tested on a range of reference sensitizers (cutaneous and respiratory sensitizers, irritants and non-sensitizers). The BMDC of our model, while exposed to sensitizers, were able to activate TC in coculture. Finally, preliminary tests using the cells of C57BL6/J mice in our coculture model showed that similar results to those obtained with cells from the BALB/c strain. The models of BMDC cultures and BMDC-TC coculture are promising for the development of alternative methods to animal experimentation assessing the sensitizing potential of chemicals
38
Klar, Richard [Verfasser], Iris [Akademischer Betreuer] [Gutachter] Antes, Bernhard [Gutachter] Küster e Angela [Gutachter] Krackhardt. "Identification of naturally presented HLA ligands on the surface of healthy and malignant hematopoetic cells and their therapeutic potential as targets for TCR-transgenic T cells / Richard Klar ; Gutachter: Bernhard Küster, Iris Antes, Angela Krackhardt ; Betreuer: Iris Antes". München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1125018143/34.
Testo completo
39
Winter, Sarah. "Identification and characterization of new genetic defects involved in Epstein-Barr virus immune response and T-cell proliferation Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility RASGRP1 is a negative factor of EOMES expression in T cells in association with an exhausted phenotype IL-27RA deficiency in humans, a new cause of susceptibility to Epstein-Barr virus infection Association of bi-allelic loss-of-function mutations in PIK3CD and TNFRSF9 causes fatal chronic active Epstein-Barr virus infection with T-cell lymphoproliferation". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB180.
Testo completoAbstract (sommario):
L'infection par le virus d'Epstein-Barr (EBV) touche plus de 90% de la population mondiale et est dans la majorité des cas asymptomatique dans l'enfance. Certains individus, souvent à l'adolescence, développent une primo-infection symptomatique appelée mononucléose infectieuse. L'EBV peut également entraîner chez des individus immunodéprimés des désordres lymphoprolifératifs, des lymphomes ou syndromes d'activation lymphohistiocytaire. Depuis une trentaine d'années plusieurs déficits immunitaires primitifs entraînant une susceptibilité particulière à l'infection par l'EBV ont été identifiés ; parmi ceux-ci figurent les déficits en SAP, XIAP, ITK, MAGT1, CTPS1, CD27 ou CD70. Leur caractérisation a permis de mettre en évidence de nouveaux mécanismes immunitaires impliqués dans la réponse anti-EBV. L'objectif de ce travail a donc été d'identifier de nouveaux défauts génétiques entraînant une susceptibilité particulière à l'infection par l'EBV. Au sein de deux familles consanguines, trois patients ont développé des lymphomes B liés à l'EBV ainsi que des épisodes de lymphoproliférations également liées à ce virus. Deux mutations homozygotes dans RASGRP1 entraînant un stop prématuré, A638GfsStoXp16 et S314X ont été respectivement identifiées par séquençage d'exome (WES) chez ces deux familles. Sur le plan immunologique ces patients sont caractérisés par une lymphopénie CD4+, un défaut de cellules T naïves, une accumulation de cellules T effectrices mémoires et une absence de cellules MAIT et iNKT. RASGRP1 est une protéine de la famille des facteurs d'échange nucléotidiques fortement exprimée dans les lymphocytes T et NK. Elle active la petite protéine G Ras qui elle-même va activer la cascade des kinases Raf-MEK-ERK (ou cascade des MAP kinases). L'analyse des cellules du patient ou de cellules de contrôles sains dans lesquelles l'expression de RASGRP1 a été inhibée par RNA interférents a permis de mettre en évidence le rôle fondamental de RASGRP1 dans la prolifération lymphocytaire T et l'expression de gènes impliqués dans cette prolifération tels que CTPS1, PCNA ou RECQL4. A l'inverse, RASGRP1 semble être un régulateur négatif du facteur de transcription EOMES impliqué dans la différenciation des lymphocytes T. EOMES est retrouvé surexprimé dans les lymphocytes T en l'absence de RASGRP1, pouvant expliquer le phénotype effecteur mémoire et sénescent des lymphocytes des patients déficients en RASGRP1. Au sein d'une autre famille consanguine, chez deux patients ayant développé une primo-infection à l'EBV symptomatique, dont l'un a nécessité un traitement par anti-CD20 et corticoïdes, a été identifiée une mutation homozygote non-sens dans IL27RA entraînant un codon stop précoce (G96X) et une absence d'expression protéique dans les cellules T des patients. IL-27RA code pour la sous-unité alpha du récepteur à l'IL-27 impliqué dans la prolifération des lymphocytes T et le développement Th1 des lymphocytes CD4+ via la cascade des JAKs/STATs. Dans les lymphocytes T des patients, l'activation de la voie JAK/STAT par l'IL-27 est complètement abolie et l'IL-27 n'augmente pas leur prolifération en réponse à une stimulation anti-CD3 (au contraire des cellules contrôles issues de donneurs sains). De plus, un défaut fonctionnel de la voie Th1 est retrouvé chez un des deux patients. Ces résultats démontrent que la voie dépendante de l'IL-27RA est déficiente chez ces deux patients et que ce défaut génétique rend vraisemblablement compte de leur immunodéficience. La description de ces deux nouveaux déficits immunitaires caractérisés par une susceptibilité à l'EBV a permis de confirmer le rôle fondamental dans l'étape de prolifération et d'expansion des lymphocytes T au cours de la réponse immune anti-EBV, mais également de mettre en évidence de nouveaux mécanismes et facteurs impliqués dans cette étapeEpstein-Barr virus (EBV) is a gamma-herpes virus that infects 90% of humans without any symptoms in most cases. Some individuals, mostly adolescents, can develop infectious mononucleosis. In immunocompromised individuals, EBV can lead to lymphoproliferative disorders, lymphomas or virus-associated hemophagocytic syndrome. In the past 30 years, several primary immunodeficiencies associated with a high risk to develop EBV-associated disorders have been identified, including SAP, XIAP, ITK, MAGT1, CTPS1, CD27 or CD70 deficiencies. Their characterization has highlighted specific pathways required for efficient immunity to EBV. The objective of this work was to identify new genetic defects associated to a peculiar susceptibility to EBV infection. In two consanguineous families 3 patients developed EBV-associated B cell lymphomas and other EBV-associated lymphoproliferative disorders. By while exome sequencing (WES) we identified two homozygous mutations in RASGRP1 leading to a premature stop codon (A638GfsX16 and S314X). Immunologically these patients presented with CD4+ lymphopenia, low number of naïve T cells and absence of MAIT and iNKT cells. RASGRP1 codes for a diacylglycerol-regulated exchange factor preferentially expressed in T and NK cells, which acts as an activator of the small G protein RAS and the downstream RAF-MEK-ERK kinases cascade (or MAP kinases pathway). Analysis of patients' T cells or control T cells in which RASGRP1 expression was downregulated by short-hairpin RNA technique has highlighted the crucial role of RASGRP1 in T cell proliferation and in the expression of genes known to be involved in cell proliferation or replication such as CTPS1, PCNA or RECQL4. Furthermore, RASGRP1 seems to be a negative regulator of the transcription factor EOMES involved in T cell differentiation. EOMES was found overexpressed in T cells in the absence of RASGRP1. This might explain the skewed effector-memory and exhausted phenotype observed in RASGRP1-deficient patients. In another large consanguineous family two patients developed symptomatic EBV primary infection requiring for one or them anti-CD20 and corticosteroids treatment. Homozygous nonsense mutation leading to a premature stop codon in IL-27RA (G96X) was identified by exome sequencing. No protein expression could be detected in patients' cells. IL-27RA codes for the subunit of IL-27 receptor involved T cell proliferation and Th1 CD4+ development through JAKs/STATs pathway. Stimulation of patients' T cells with IL-27 led to absent JAK/STAT activation pathway and did not enhance their proliferation after anti-CD3 stimulation (contrary to healthy control T cells). Furthermore, Th1 functional defect was found in one patient. These results demonstrate that IL-27RA pathway is deficient is these two patients and that this genetic defect causes their immunodeficiency. Characterization of these two new primary immunodeficiencies associated with a high susceptibility to EBV infection has confirmed the crucial role of T cell proliferation and activation in EBV immune response but has also highlighted new pathways involved in T cell expansion
40
Schadeck, Eva Barbara. "Identification of cytotoxic T cell epitopes on measles-virus nucleoprotein". Thesis, London School of Hygiene and Tropical Medicine (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285192.
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41
Angove, Helen Louise. "The identification of bluetongue virus T-cell epitope(s) in sheep". Thesis, University of Hertfordshire, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260772.
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Geiger, Rebekka. "Analysis of the human naïve T cell repertoire and identification of a novel T helper subset". [S.l.] : [s.n.], 2009. http://www.zb.unibe.ch/download/eldiss/09geiger_r.pdf.
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Grotel, Martine van. "Identification of prognostic genetic factors in pediatric T-cell acute lymphoblastic leukemia". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13286.
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Holderness, Kathryn. "Identification of immunodominant T cell epitopes from enterotoxigenic E. coli colonization factor antigen I (CFA/I) responsible for T helper cell cytokines". Thesis, Montana State University, 2012. http://etd.lib.montana.edu/etd/2012/holderness/HoldernessK0512.pdf.
Testo completoAbstract (sommario):
Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal disease contracted by consuming contaminated food or water. ETEC is able to adhere to the small intestine by utilizing pili or fimbriae, one of which is the fimbriae Colonization Factor Antigen/I (CFA/I). The extracellular portion of CFA/I fimbriae is comprised of two fimbrial subunits, cfaB and cfaE. Expression of CFA/I fimbriae on the surface of an attenuated Salmonella vaccine vector, Salmonella-CFA/I, results in a biphasic T cell response in immunized mice. This response is characterized by the initial production of Th2-type cytokines, including IL-4 and IL-5, followed by a shift after 4 weeks toward an IFN-gamma-associated, Th1 response. Restimulation of CD4 + T cells from Salmonella-CFA/Iimmunized mice with CFA/I fimbriae also generates the anti-inflammatory cytokine, IL-10. Salmonella-CFA/I is able to generate antigen-independent Foxp3 + regulatory T cells, which are able to reduce symptoms of Experimental Autoimmune Encephalomyelitis in immunized SJL mice and Collagen Induced Arthritis in DBA/I and C57BL/6 mice, via production of IL-10 and TGF-beta by phenotypically distinct regulatory T cell subsets. The following research describes the contribution of cfaB and cfaE to the observed therapeutic and immunological responses. This was measured by independently expressing recombinant cfaB and cfaE proteins and evaluating the associated cytokine responses from the co-culture of these proteins with CD4 + T cells from immunized mice. Major Histocompatibility Complex II-restricted immunodominant regions were also mapped for both cfab and cfae proteins using cytokine ELISAs, ELISPOTs, Proliferation Assays, and flow cytometry. We mapped an IFN-gamma-producing peptide from cfaB and an IL-4-producing peptide from cfaE. We further determined that co-culture with peptides from both fimbrial proteins is able to generate regulatory T cell-associated cytokines including IL-10 and TGF-beta as well as the newly described suppressive cytokine, IL-35. These results show that the immune responses to cfaB and cfaE are mediated by multiple immunodominant regions within each protein.
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Pang, Ha Sang. "Identification of CD8+ T cell epitopes from HCA661 presented by HLA-A2 molecules /". View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202006%20PANG.
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46
Phillips, Rhian Medi. "Identification of high endothelial cell-derived chemokines that regulate T lymphocyte transendothelial migration". Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392046.
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47
Kennah, Erin. "Identification of differentially expressed genes in AHI-1-mediated leukemic transformation in cutaneous t-cell lymphoma". Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/962.
Testo completoAbstract (sommario):
The oncogene Ahi-1 was recently identified through provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in several leukemic cells lines, particularly in cutaneous T-cell lymphoma (CTCL) cell lines (Hut 78 and Hut 102). Hut 78 is derived from a patient with Sezary syndrome, a common leukemic variant of the human CTCL mycosis fungoides. Aberrant expression of AHI-1 mRNA and protein has been found in CD4⁺CD7⁻ leukemic Sezary cells from patients with Sezary syndrome. Moreover, stable suppression of AHI-1 using retroviral-mediated RNA interference in Hut 78 cells inhibits their transforming activity in vitro and in vivo. In an effort to identify genes involved in AHI-1-mediated leukemic transformation in CTCL, microarray analysis was performed to compare six RNA samples from AHI-1 suppressed Hut 78/sh4 cells to five samples from Hut 78 control cells. Limma and dChip analyses identified 218 and 95 differentially expressed genes, respectively, using a fold change criteria of > or < 2 and a p-value threshold of ≤ 0.01. After evaluation of both analyses, 21 genes were selected based upon interesting structural and functional information, specificity to hematopoietic cells or T-cells, and previous connections to cancer. Expression patterns of these 21 genes were validated by qRT-PCR with p-values < 0.05 ranging from 1.97 x 10⁻¹⁰ to 6.55 x 10⁻³, with the exception of BRDG1 at 5.88 x 10⁻². The observed up-regulation of both BIN1 and HCK in AHI-1 suppressed Hut 78/sh4 cells as compared to control cells further confirmed at the protein level. The tumor suppressor BIN1 is known to physically interact with c-MYC, which also exhibits differential protein expression in these cells. Characterization of BIN1 identified 4 isoforms all of which contain exon 10 and demonstrate alternative splicing of exons 12A and 13. Additionally, qRT-PCR results from primary Sezary samples indicate there is clinical significance in the expression changes detected for BIN1, HCK, REPS2, BRDG1, NKG7 and SPIB. These findings identify several new differentially expressed genes that may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells.
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Tolmie, Helen. "Isolation of S100B from the cytosol of a T lymphocyte cell line : identification of receptor proteins". Thesis, Liverpool John Moores University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247725.
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Walsh, Claire. "Human T-cell leukaemia virus type 1 tax oncoprotein identification of novel celluar interaction partners". Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499848.
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Reiser, Michael [Verfasser]. "Identification and characterization of immunodominance hierarchies within vaccine-relevant CD8 T cell responses / Michael Reiser". Ulm : Universität Ulm. Medizinische Fakultät, 2012. http://d-nb.info/1020449500/34.
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