Добірка наукової літератури з теми "Tcell"
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Статті в журналах з теми "Tcell"
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Schalck, Aislyn, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara Hughes, Shanshan Bai, Min Hu, et al. "Abstract 2847: Simultaneous TCR and transcriptomic sequencing of single Tcells defines biological subtypes in pancreatic cancer for adoptive Tcell therapy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2847. http://dx.doi.org/10.1158/1538-7445.am2022-2847.
Повний текст джерелаАнотація:
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal tumor-type with very few effective treatment strategies. Attempts to improve outcomes using immune checkpoint blockade therapy have also failed, likely because the overall Tcell infiltration in this tumor-type is low. Despite this, the presence of CD3+CD8+ tumor-infiltrating lymphocytes (TIL) in PDAC is associated with improved survival outcomes, suggesting that other immune-based strategies could be more successful. Here, we examine ex vivo tumor-infiltrating Tcell expansion for adoptive Tcell therapy (ACT) as a potential strategy for treating PDAC. The focus of this study is to understand the transcriptional states of Tcells in the pancreas and PDACs and how they change with ex vivo expansion and re-infusion into patients as treatment strategy. We have performed both single cell transcriptome and TCR sequencing (scRNA-TCRseq) on 54,579 Tcells from 8 human PDAC samples and the ex vivo grown TIL from a subset of 6 patients and found 13 purported substates. Through TCR tracking of the Tcell clonotypes, we find that the expansion protocol is able to expand Tcells found in many different Tcell states in the primary tumor. Furthermore, we compared our thirteen tumor-infiltrating substates with 41,935 Tcells from two other independent single cell studies across 71 samples, and confirmed our substates to be present across all datasets. Citation Format: Aislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara Hughes, Shanshan Bai, Min Hu, Tapsi Kumar, Mark Hurd, Matthew Katz, Chine-Wei Tzeng, Shubham Pant, Milind Javle, Anirban Maitra, Cara Haymaker, Michael Kim, Nicholas Navin, Chantale Bernatchez. Simultaneous TCR and transcriptomic sequencing of single Tcells defines biological subtypes in pancreatic cancer for adoptive Tcell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2847.
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Florek, Mareike, Emanuela I. Sega, Antonia MS Mueller, Dennis B. Leveson-Gower, Judith A. Shizuru, and Robert S. Negrin. "A Novel Model of Pre-Emptive ECP Treatment Shows Significant Reduction of Gvhd-Related Mortality In Mice,." Blood 118, no. 21 (November 18, 2011): 4025. http://dx.doi.org/10.1182/blood.v118.21.4025.4025.
Повний текст джерелаАнотація:
Abstract Abstract 4025 Graft versus host disease (Gvhd) remains the major cause of morbidity and mortality after bone marrow transplantation (BMT). To prevent Gvhd the graft has to be rendered tolerant to avoid alloreactivity towards the host. One promising approach to induce tolerance in the graft is to administer apoptotic cells to the host. Apoptosis can be induced by extracorporeal photopheresis (ECP), a therapy based on exposure of cells to photoactivable 8-methoxypsoralen (8MPO) and UVA irradiation. The effect of ECP treatment is at least in part, due to alteration of dendritic cell (DC) maturation, leading to reduced antigen presentation and Tcell activation. Moreover, ECP treatment increases the number of regulatory Tcells (Treg), further reducing Tcell activation. In contrast to clinical practice where ECP is only applied to established Gvhd, we have developed a pre-emptive murine model with the aim of inhibiting the initiation phase of acute Gvhd and improving survival. Here we describe our model and characterization of the mechanisms of action. Apoptotic host-type splenocytes were infused into MHC matched or mismatched recipients 5 and 2 days prior to lethal irradiation and BMT. Apoptotic cells were generated by incubation with 8-MPO and UVA light (UVAR light set, Therakos). Mice were followed for Gvhd score and survival. ECP-treated mice survived longer both across major (median survival 51 versus 26 days, p<0.0001) and minor (median survival 56.5 versus 9 days, p<0.002) histocompatibility barriers. Importantly, even though ECP treatment promoted tolerance against the host it did not impact the graft versus tumor effect in a B-cell lymphoma model. To address the mechanisms of this beneficial outcome we investigated Tcell proliferation in vivo (i), ex vivo (ii) and in vitro (iii). (i) Luciferase-expressing Tcon were used to quantify Tcell proliferation in vivo by bioluminescent imaging. ECP-treated mice showed reduced CD4+Tcell proliferation during the initiation phase of Gvhd (day+4) compared to mice receiving Tcon only. (ii) Re-isolation of CFSE labeled Tcon on day+4 after BMT showed a reduction in CD4+Tcell proliferation. (iii) FACS-sorted DC incubated with apoptotic cells for 2 days in vitro showed a diminished capability to induce Tcell proliferation. To evaluate the impact of ECP treatment on the expression of homing (P-Selectin, α4β7) and activation (CD44, CD69) markers on donor Tcells we performed re-isolation experiments on day+3 and day+7. At day +3 ECP-treated groups showed a reduced expression of these markers in comparison to control groups. These studies demonstrate slower trafficking to Gvhd target organs. Furthermore, at day+7 ECP-treated groups showed increased FoxP3-expressing host Tregs in comparison to control groups whereas donor Treg were similar in both groups. Ongoing experiments will utilize a mouse model in which it is possible to selectively deplete either donor or host Tregs to examine the role of these two subpopulations of Treg in improving Gvhd outcome. In summary, ECP treatment prior to transplantation led to (i) a significant survival benefit with no impact on graft versus tumor effect; (ii) reduced CD4+ Tcell proliferation; (iii) delayed expression of homing and activation markers during the initiation phase of Gvhd and (iv) an increase in host Treg. Overall our work suggests that pre-emptive ECP of host cells prior to BMT may be a clinically relevant strategy to prevent acute Gvhd. Disclosures: No relevant conflicts of interest to declare.
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Kennedy, Steven C., Alison J. Johnson, Alessandro Sette, John Chan, William R. Jacobs, and Steven A. Porcelli. "M. smegmatis vaccination reveals the mycobacterial ribosome as a potential CD4+ Tcell enhancing vaccine target." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 65.10. http://dx.doi.org/10.4049/jimmunol.196.supp.65.10.
Повний текст джерелаАнотація:
Abstract Mycobacterium tuberculosis(Mtb) is an airborne pathogen that infects one third of the world’s population. To date no vaccine has had major success in reducing the enormous global burden of disease from this infection. Critical to the control of Mtb is the ability of a vaccine to induce a strong CD4+ Tcell response. The currently available vaccine, M. bovis BCG, is of limited efficacy, potentially due to its retention of immune evasion mechanisms that actively inhibit the host presentation of critical antigens to CD4+ Tcells. Examining antigens that are hidden during a BCG immunization may lead to identification of novel vaccine targets. Our lab has previously identified an M. smegmatis based vaccine, IKEPLUS, which elicits a strong CD4+ Tcell response leading to significantly enhanced protection to Mtb over BCG vaccination. M. smegmatis is a non-pathogenic mycobacterium that has not retained the ability to disrupt antigen presentation to the host immune system. Examination of the CD4+ Tcell response to IKEPLUS and BCG has identified the mycobacterial ribosome as a major immunogenic target in the M. smegmatis based IKEPLUS, but not in BCG. This dichotomy in the immune response led us to further characterize the ribosome and evaluate its protein constituents as potential vaccine targets. The ribosome is composed of 57 individual proteins; of these 57 proteins, we have identified 20 as immunogenic, and identified minimal CD4+ Tcell epitopes for 10 of the 20 identified proteins. These findings have led us to begin development of a mycobacterial ribosome based vaccine to enhance the currently existing BCG regimen. This approach will allow us to complement what we believe is a critical flaw of BCG while retaining the widely used BCG vaccination regimen.
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Davidson, Tom, Willy Hugo, Anthony Wang, Jiyoon Kim, Gang Li та Robert Prins. "IMMU-30. UPREGULATED T CELL AND INTERFERON-Γ-RELATED GENE EXPRESSION IS ASSOCIATED WITH INCREASED SURVIVAL IN RECURRENT PEDIATRIC HIGH-GRADE GLIOMA". Neuro-Oncology 22, Supplement_3 (1 грудня 2020): iii365—iii366. http://dx.doi.org/10.1093/neuonc/noaa222.384.
Повний текст джерелаАнотація:
Abstract Recurrent pediatric high-grade glioma (pHGG) is the leading cause of cancer-related mortality in children. Immunotherapy is a successful treatment approach for a growing number of cancers and is being investigated as a treatment strategy for pHGG. Immunotherapy has shown the most benefit in tumors with increased infiltrating T cells at baseline. Our recently published results revealed that neoadjuvant checkpoint inhibition in recurrent adult glioblastoma was associated with upregulation of a T cell and interferon-γ-related gene expression signature (Tcell-IFNγGES) and was correlated with a significantly extended overall survival (OS). In this study, we examined the immune landscape in recurrent pHGG and the association of Tcell-IFNγGES in the tumor with survival. We analyzed tumor RNAseq data collected at time of recurrence from a historical cohort of 42 pHGG patients from the Children’s Brain Tumor Tissue Consortium. We found a significant transcriptional enrichment of Tcell-IFNγGES in 54% of the tumors. The survival of patients with high Tcell-IFNγGES was observed to be significantly higher than patients with low Tcell-IFNγGES, (log-rank p=0.05). The 3-year OS for patients with low versus high Tcell-IFNγGE was 28.5% (95%, CI:13.7%-59.5%) compared to 50.2% (95%, CI:33.1%-76.1%). When patients were stratified by age, gender and race, low Tcell-IFNγGES was found to be a poor OS prognostic factor (hazard ratio=2.4 (1.14–5.14), p=0.02). This indicates a strong relationship of decreased Tcell-IFNγGES and increased risk of death. Future investigations are necessary to validate these findings, and to explore the value of Tcell-IFNγGES as a predictive biomarker for response to immunotherapy in pHGG.
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Darwiche, Sophie, Yanting Wang, John Brumfield, Sladjana Stratimirovic, Kathryn Vreeland, Ana Botero, Sylvia Martinez, et al. "Heme oxygenase-1/CO protect against post-traumatic suppression of adaptive immune responses (IRC8P.475)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 190.3. http://dx.doi.org/10.4049/jimmunol.192.supp.190.3.
Повний текст джерелаАнотація:
Abstract Traumatic injury induces a systemic dysregulated immuno-inflammatory response that contributes to mortality. This response includes an upregulation of pro-inflammatory cytokines by innate cells and an independent suppression of adaptive immunity characterized by reduced Th1 responses. Heme oxygenase-1 (HO-1) and its byproduct, carbon monoxide (CO), are protective against injury-induced inflammation and end-organ damage, but their beneficial role in the dysregulation of adaptive responses following trauma is unknown. To investigate this, B6 mice received multiple-trauma or no manipulation, and were given either vehicle or a HO-1 inducer (Cobalt protoporphyrin, CoPP; 5mg/kg) prior to injury. Another cohort received either room air or CO (250ppm) for 4 hours directly post-injury. At 48hr post-trauma, Tcell functions were assessed by ex-vivo mitogen-induced Tcell proliferation and Th1 cytokine release (IL-2 and IFN-γ). As expected after injury, a near 50% reduction in Tcell proliferation was seen in vehicle- or air-treated trauma mice, compared to uninjured controls (p=0.007). A parallel reduction in Tcell IL-2 and IFN-γ release was observed. In clear contrast, CoPP or CO treatment prevented trauma-induced reductions in Tcell proliferation and cytokine release (fold difference 0.90±0.10 and 1.21±0.16 to uninjured controls, respectively). Overall, HO-1 represents an endogenous protective pathway that can be exploited following trauma to preserve normal immune functions & survival.
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Khichade, Monika D., Dr Sameer Shafi, Priyanka S. Nilangekar, Aishwarya S. Gandhle, Mohini A . Gurav, and Vishal B. Phulsundar. "Immunotherapy in Cancer: Biology Therapy." Journal of Biomedical and Pharmaceutical Research 11, no. 5 (November 14, 2022): 62–73. http://dx.doi.org/10.32553/jbpr.v11i5.937.
Повний текст джерелаАнотація:
Abstract:
The relationship between immune system and cancer has progressively increased in the last few years. Recent advancement in treating cancer immunotherapy includes monoclonal antibodies, adaptive cancer therapy; monoclonal antibodies have came into force. General therapies include surgery, radiation and chemotherapy etc... Beyond that the immunotherapy in treating cancer helps our immune system to fight against tumor forming cell, which acts as an example of precision medicine .It mainly targets tumor in filtering lymphocytes, CAR Tcells, TCR Tcell etc…. Personalized combination therapy stands as promising stratergy for upcoming cancer treatment, personalized medicines includes patient derived tumor cell DNA oncolytic viruses dendritic cells etc.
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Heald, Peter, Jo-Ann Latkowski, Lynn D. Wilson, and Lawrence A. Mark. "Successful therapy of cutaneous Tcell lymphoma." Expert Review of Dermatology 3, no. 1 (February 2008): 99–110. http://dx.doi.org/10.1586/17469872.3.1.99.
Повний текст джерела
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Nguyen, Vy Tuong, Nhung Thi Tuyet Do, Thuong Thi Thuong Nguyen, and Trung Lap Huynh. "Effect of the reduced-graphene oxide on the structure and thermal properties of compoiste PMMA/micro-cellulose fibers from petioles of Vietnamese nipa palm tree." Science and Technology Development Journal 19, no. 4 (December 31, 2016): 202–11. http://dx.doi.org/10.32508/stdj.v19i4.682.
Повний текст джерелаАнотація:
This study separated and treated successfully micro-cellulose fibers from petioles of Vietnamese nipa palm tree (tCell) by simple mechanical and chemical methods. The combination of the treated micro-cellulose fibers and reduced-graphene oxide by hydrazine hydrate (tCell-RGO) increases the thermal stability and the glass transition temperature of polymethylmathacrylat (PMMA) in synthesis composite by in situ emulsion method. The study improves the environmental friendliness of PMMA and overcome the disadvantages of low thermal decomposition of cellulose in preparation of polymer composites, especially kinds of heat-stable polymers as PMMA.
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Santamaria, P. "Transgenic animal expressing diabetogenic Tcell receptor transgenes." Biofutur 1997, no. 167 (May 1997): 48. http://dx.doi.org/10.1016/s0294-3506(99)80369-x.
Повний текст джерела
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Faulkner, Matthew F., and Jeannine M. Durdik. "Age-associated defects in Tcell metabolism (46.10)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 46.10. http://dx.doi.org/10.4049/jimmunol.182.supp.46.10.
Повний текст джерелаАнотація:
Abstract Aging at the cellular and molecular level causes a decline in immune function. We are characterizing the responses of naïve T-cells to activation. Activated T-cells of aged mice initiate proliferation as well as their young counterparts, but have increased apoptotic rates. However, the mechanisms behind this post- activation death are not completely understood. We will show alterations in metabolic activities in T-cells of aged mice through differences in the expression of glucose transporter (Glut 1), glucose uptake and lactate production. Additionally, we will correlate these findings with autophagocytic vesicle formation by analyzing microtubule-associated protein -1 light chain 3 (LC3) as well as comparing relative amounts of actively respiring mitochondria using Mitotracker Red CM-H2XRos, a membrane potential dependant dye, and total mitochondrial mass by staining with the mitochondrial-selective fluorescence label Mitotracker Green. Levels of reactive oxygen species will be then quantified by staining with ROS specific dye DCF-DA and correlated to the ratio of mitochondrial mass to membrane potential.
Дисертації з теми "Tcell"
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Gardner, Leanne M. (Leanne Margaret) 1977. "Modulation of the allergen-specific Tcell response." Monash University, Dept. of Pathology and Immunology, 2003. http://arrow.monash.edu.au/hdl/1959.1/5817.
Повний текст джерела
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Anis, Mursalin M. "Modulation of naive CD4+ Tcell activation and dendritic cell function in the lungs during pulmonary mycobacterial infection." Connect to text online, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1184427168.
Повний текст джерела
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Gavriil, Artemis. "Chimeric antigen receptor (CAR) T-cell immunotherapy for MUC1-positive breast cancer." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/chimeric-antigen-receptor-car-tcell-immunotherapy-for-muc1positive-breast-cancer(3d56d668-10c0-418e-a2b9-2010edd51234).html.
Повний текст джерелаАнотація:
Cancer immunotherapy using chimeric antigen receptor (CAR) T-cells has shown exceptional promise in the treatment of patients with refractory B-cell malignancy. In this approach, patient-derived peripheral blood T-cells are engineered to express a cell surface receptor, which confers specificity for a tumour-associated (TA) antigen. Mucin-1 (MUC1) is a large transmembrane glycoprotein that is overexpressed in 90% of breast cancers. A further important characteristic of this mucin is the fact that it is under-glycosylated in cancer cells. This holds the potential for CAR T-cell mediated targeting of MUC1 epitopes in tumour-cells which are not exposed in normal cells. Antibodies such as TAB004 and HMFG2 are considered to bind preferentially to TA-MUC1. The aim of this PhD project was the development of a CAR Tcell approach for MUC1-positive breast cancer. Herein, the anti-tumour potential of a novel 2nd generation MUC1-specific CAR, named TAB28z, has been investigated. The binding domain of this CAR is derived from the TAB004 anti-MUC1 antibody. TAB28z is being compared with two other previously developed MUC1-specific CARs, H28z and HDF28z, both of which are derived from the HMFG2 antibody. TAB28z CAR T-cells demonstrated significant anti-tumour activity against MUC1-positive breast cancer cell lines in the in vitro setting. Nevertheless, it became apparent throughout this project that MUC1 expressed on activated T-cells is detected by both HMFG2-based and TAB004-based CAR T-cells during the T-cell expansion period. This background recognition resulted in tonic signalling by CARs, which was accompanied by constitutive production of IFN-γ, CAR T-cell enrichment, reduced T-cell expansion and a trend towards upregulation of T-cell activation and exhaustion markers. Despite these observations, the activity of the three MUC1-specific signalling CARs was investigated in two different breast cancer xenograft models. No significant anti-tumour responses were observed in either of the two models, which could possibly be attributed to the effects of tonic signalling.
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Cardone, John. "CD46-mediated signals in the regulation of T-cell cytokine production and intestinal wound healing." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/cd46mediated-signals-in-the-regulation-of-tcell-cytokine-production-and-intestinal-wound-healing(4b3dcd9c-8cfa-4fe4-80fc-2bda8ef31bfe).html.
Повний текст джерелаАнотація:
Complement is a key part of innate immunity and vital in the first line of defence against invading pathogens. The understanding of the role of complement in the host’s immune defence has undergone its first major change when it became clear that complement is also required for the optimal induction and function of adaptive immunity, particularly B cell activation and T cell effector responses. It is now also becoming increasingly clear that complement plays a key role in the contraction of T cell responses and thus, by definition, in immune homeostasis. The first part of this thesis focuses on such least understood role of complement. Firstly, evidence is reported for a novel mechanism by which the complement regulatory protein CD46 regulates the key T helper type 1 cytokine IFN-y and the canonical immunosuppressive cytokine IL-10. The production of both IFN-y and IL-10 is shown to be temporally regulated by TCR and CD46 signals in CD4+ T cells in an IL-2-dependent fashion and is shown to be defective in rheumatoid arthritis patients. The molecular pathways linked to the CD46-induced switch of TR! cells are largely undefined and were investigated. Gene array studies highlighted the asparagine endopeptidase (AEP) as a candidate molecule involved in the regulation of the switch of TH1 cells towards IL-10 production. The CD46-driven IFN-y secretion, but not the intracellular expression, was found to be substantially reduced by AEP inhibition; IL-10 production was consequently affected confirming the importance of IFN-y signalling in the CD46-induced "switch" mechanism. The cytokines produced by T cells activated via CD46 may also be important in the crosstalk with surrounding tissues. Here the functional consequences of CD46 signals were further investigated in the context of intestinal epithelial cells to allow the discrimination of the effects of CD46 signals in the two different cells types. A novel role for CD46 in the promotion of cellular proliferation and wound healing was reported.
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Thayaparan, Thivyan. "Development of c-Met targeted chimeric antigen receptor T-cell immunotherapy for malignant pleural mesothelioma." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/development-of-cmet-targeted-chimeric-antigen-receptor-tcell-immunotherapy-for-malignant-pleural-mesothelioma(0b08a5d1-8a96-4393-baa2-30219dbd8d87).html.
Повний текст джерелаАнотація:
Malignant pleural mesothelioma (MPM) is an incurable cancer that commonly presents at an advanced stage. Although surgery, chemotherapy and radiotherapy treatment may be used, median survival from diagnosis is less than 12 months. Consequently, new therapeutic approaches are essential. Chimeric antigen receptors (CARs) are fusion molecules that couple the HLA-independent binding of a cell surface target to the delivery of a tailored T-cell activating signal. The receptor tyrosine kinase c-Met is overexpressed in >80% of MPM making it an attractive candidate for CAR T-cell immunotherapy. To target c-Met, three candidate CARs were developed named N28z, M28z and cM28z. All contained a CD28/CD3ζ endodomain fused to one of three stabilised peptides based on the N and K1 domains of hepatocyte growth factor, which is the only natural ligand for c-Met. Specificity and functionality of c-Met re-targeted CAR+ T-cells was confirmed by co-cultivation with c-Met-expressing NIH 3T3 and MPM cell lines. This was indicated by target-dependent cytotoxicity and enhanced cytokine release (IL-2 and IFN-γ), when compared to appropriate controls. Anti-tumour activity of all three candidate CARs could be further enhanced by pre-treatment of tumour cells with poorly cytotoxic doses of chemotherapy (cisplatin and pemetrexed) or by co-incubation with the PD-1 blocker, pembrolizumab. No differences between function of the three candidate CARs were evident in these studies. To evaluate in vivo anti-tumour activity, an intraperitoneal MPM xenograft model was established that was amenable to monitoring using bioluminescence imaging. Candidate c-Met re-targeted CARs were coexpressed with the chimeric cytokine receptor, 4αβ, enabling IL-4 mediated, selective enrichment of CAR+ T-cells. In mice with an established tumour burden, I found that cM28z/4αβ+ T-cells were superior to other c-Met re-targeted or control T-cells in eliciting sustained disease control. Together, these findings demonstrate proof of concept for the utility of c-Met re-targeted CAR+ T-cells to recognise and destroy mesothelioma tumour cells.
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Yallop, Deborah. "Characterisation of the T-cell component of the lymph node microenvironment in chronic lymphocytic leukaemia." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/characterisation-of-the-tcell-component-of-the-lymph-node-microenvironment-in-chronic-lymphocytic-leukaemia(d86db73f-e728-4dde-b035-2bf4a9d6612c).html.
Повний текст джерелаАнотація:
The aim of this thesis was to characterise the T-cell component of the lymph node (LN) microenvironment in chronic lymphocytic leukaemia (CLL). It is well established that the proliferation of the neoplastic clone in CLL occurs primarily within the secondary lymphoid tissues and that within LNs these cells are in close contact with T-cells and other elements of the microenvironment. First I present a phenotypic study of the T-cells of the CLL LN obtained by fine needle aspiration. I found that, compared to CLL peripheral blood (PB), CLL LNs contain an excess of effector memory CD4+ T-cells and that the LN T-cells express more PD-1 than those from the PB; suggesting ongoing activation. Multiparameter immunofluorescence microscopy on LN biopsy sections showed that proliferating Ki67+ CLL cells are in contact with CD4+ PD-1+ T-cells. Next I sought to characterise the T-cell receptor (TCR) repertoire of flow sorted LN and PB CD4+ T-cells by spectratyping. This revealed oligoclonality in both compartments, with a significant reduction in TCR diversity in the PD-1hi subset. All subsets were skewed compared to healthy age matched PB. The spectratype profiles were distinct between the LN and PB and therefore likely a result of interaction with different antigens. This data was complemented by high throughput sequencing of the TCR, which showed more sequence overlap between 2 LNs taken from the same CLL patient, than between the LN and PB. Finally I present a preliminary in-vitro study aimed at recapitulating the events in CLL LNs. This study showed that PD-L1 can be upregulated on PB CLL cells by CD3/CD28 stimulation of accompanying T-cells, and that blocking PD-1 can lead to increased secretion of interferon gamma. Taken together these findings suggest that CLL CD4+ T-cells are subject to chronic activation and have undergone antigen driven oligoclonal expansion within the LN.
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Navas, Pérez Enrique. "Una nueva domesticación molecular en el origen de los euterios: la familia génica Bex/Tceal." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/406392.
Повний текст джерелаАнотація:
Uno de los mecanismos genéticos que facilitan la innovación evolutiva es la formación de nuevos genes. De entre los procesos que permiten generar nuevos genes, la domesticación molecular de genes transposónicos es uno de los más desconocidos. Sin embargo, los transposones domesticados (TDs) han sido cruciales para el desarrollo de innovaciones evolutivas tan relevantes como el sistema inmune adaptativo de los gnatóstomos o la placenta de los mamíferos terios. Sólo recientemente se ha intentado una identificación sistemática de TDs. El primer punto de esta tesis consistió en la búsqueda de TDs en el genoma humano, mediante un sencillo programa informático que clasificaba como candidatos a los genes cuya región codificante solapara >50% con un transposón. Uno de los candidatos identificados fue Tceal7, un miembro de la familia génica específica de mamíferos euterios Bex/Tceal. Así, pudimos trazar el origen de esta familia a la domesticación de una serie de fragmentos de retrotransposones L1 en el ancestro de los placentarios. Este es el segundo caso de domesticación molecular de un L1 en metazoos, y el primero que origina una familia multigénica.
El siguiente paso fue caracterizar el proceso de exaptación de las regiones reguladoras que permitieron el nacimiento de la familia Bex/Tceal. Así, se puso de manifiesto la relación existente entre el origen de esta familia y otros genes específicos de euterios situados en el mismo locus del cromosoma X: la familia ArmcX y el gen Hnrnph2. La región que da sentido a esta relación es el motivo BGW. Los motivos BGW de diversos genes fueron testados mediante un ensayo de transgen reportero. De este modo pudimos determinar que el motivo BGW no es la encargada de conferir especificidad de tejido a la expresión de estos genes, sino que, probablemente, es una secuencia con una elevada capacidad de sensar señales regulatorias del ecosistema genómico circundante.
En estudios recientes, las proteínas BEX han sido catalogadas como proteínas intrínsecamente desordenadas que forman hubs de interacciones proteína-proteína. El ORF de los genes Bex/Tceal deriva del extremo amino-terminal del ORF1 de un retrotransposón L1 llamado HAL1b. Esta región de la proteína transposónica se corresponde con el coiled-coil, una región típicamente desordenada. Encontramos que todas las proteínas BEX/TCEAL tienen una estructura desordenada y algunas de ellas un coiled-coil en su extremo carboxi-terminal, con lo que es altamente probable que esta característica, conservada del transposón ancestral, haya determinado la promiscuidad de estas proteínas en cuanto a sus interacciones.
Existe poca o ninguna información sobre la función de la mayoría de los genes Bex/Tceal. Por lo tanto, se decidió generar y caracterizar una línea de ratones mutantes para Bex3, uno de los miembros de esta familia. Para ello, se utilizó el sistema CRISPR/Cas9. La caracterización de una de las dos líneas de ratones mutantes arrojo una serie de alteraciones comportamentales asociadas a un comportamiento autístico, así como malformaciones esqueléticas. De forma relevante, se detectó una hiperactivación de lá vía mTOR en el encéfalo de los ratones mutantes, lo que brinda una primera pista sobre las bases moleculares del fenotipo comportamental.
Como conclusión, se ha identificado e investigado un nuevo caso de domesticación molecular de un transposón en el origen de los euterios, que dio lugar a la familia multigénica Bex/Tceal. Además, se ha generado y empezado a caracterizar el fenotipo de una línea de ratones mutante para Bex3, uno de los genes de esta familia. Queda para futuros estudios profundizar en las implicaciones evolutivas de la aparición de esta familia.One of the genetic mechanisms that facilitate evolutionary innovation is the originaton of new genes. The molecular domestication of transposable elements is among the least known sources of new genes. This study began with the design of a simple bioinformatic pipeline to identify new events of molecular domestication in the human genome. Genes with more than 50% of their coding sequence overlapping with an annotated transposon were considered as candidates. With this method we identified the Tceal7 gene, which belongs to an eutherian-specific family called Bex/Tceal. Thus, we could trace the origin of this family to the molecular domestication of L1 retrotransposon fragments in the ancestor of placental mammals. This is the second case of this kind in metazoans, and the first to give rise to a multigenic family. The next step was to characterize the exaptation process of regulatory regions that allowed the birth of this family. In this way, we could find that the origin of the Bex/Tceal family is tightly related to other eutherian-specific genes that lay in the same locus. To investigate the function of this family, we aimed to generate and characterize Bex3-mutant transgenic mice using CRISPR/Cas9 technology. We found that these mice had autistic-like behaviors and several skeletal malformations. Furthermore, the mTOR pathway was hyperactivated in the brain of adult Bex3-mutant mice. This is a first step towards the understanding of the molecular basis of the observed phenotype. In conclusion, we have identified and investigated a new molecular domestication in the origin of eutherian mammals that gave rise to the multigene family Bex/Tceal. Moreover, we have started to analyze the function of this family and the evolutionary implications of its birth.
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PERRONE, CAROLA. "Identification of common lymphoid precursors cells in tumor tissues and peripheral blood of cancer patients." Doctoral thesis, Università degli studi di Genova, 2022. http://hdl.handle.net/11567/1079638.
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PURPOSE: Identification of novel Common Lymphoid Precursors (CLP) cells in peripheral blood and tissue derived from cancer patients characterized by the expression of Lin-CD34+DNAM-1bright CXCR4+ markers and Lin-CD34-CD16+CD7- markers, previously identified in peripheral blood of patients with chronic inflammation and not found in healthy donors. In vitro culture of CLPs cells derived from tumor samples.
METHODS: Phenotypic and functional analyses on novel CLPs were performed by multiparametric cytofluorimetric assays.
RESULTS: Analysis of peripheral blood and tissue samples of cancer patients revealed the presence of Lin-CD34+DNAM-1bright CXCR4+ and Lin-CD34-CD16+CD7- inflammatory CLPs. In addition, an increase of Lin-CD34DNAM-1brightCXCR4+ inflammatory lymphoid precursors is shown in peripheral blood of cancer patients following NSCLC therapeutic treatment. Characterization of in vitro derived progenies from CLP cells derived from cancer patients highlighted the presence of mature and functional T progenies.
DISCUSSION: The identification of novel CLPs not only in peripheral blood of patients with chronic inflammation but also in peripheral blood and tissue of cancer patients (Lymphoma, Kaposi’s Sarcoma, NSCLC) suggests that these lymphoid precursors are released in peripheral blood during inflammatory condition and could be involved in tumor progression control.
CONCLUSION: The presence of precursor cells in tumor samples is a starting point for discovering their role in tumor pathogenesis.
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Marcon, Alexandre Seminoti. "Influência da espessura corneana na acuidade visual corrigida após transplante de córnea endotelial lamelar profundo (TCELP)." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-16102014-085907/.
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Objetivo: Analisar a influência da espessura corneana central na acuidade visual (AV) corrigida após transplante de córnea endotelial lamelar profundo (TCELP). Métodos: Foram estudados de forma prospectiva 155 olhos de 127 pacientes portadores de ceratopatia bolhosa ou distrofia endotelial de Fuchs no sexto mês de pós-operatório do TCELP, entre março de 2000 e março de 2005. Foram excluídos pacientes com outras alterações oculares que justificassem baixa AV. Todos os pacientes foram submetidos à avaliação oftálmica, quando foram determinadas AV corrigida, por meio de exame refratométrico, e espessura corneana central, através da paquimetria ultra-sônica. As técnicas usada foram previamente descritas. Os olhos foram agrupados de acordo com as medidas de AV: grupo I (20/20 - 20/30), grupo II (20/40 - 20/50), grupo III (20/60 - 20/80), grupo IV (20/100 - 20/400). Para correlação com paquimetria e análise estatística, as medidas de AV foram convertidas da tabela de Snellen para a tabela logarítmica (logMAR). Foram criadas variáveis categóricas para expressar status de faixa de normalidade de espessura corneana (entre 495 e 651 ?m), usando como pontos de corte valores encontrados na literatura. Resultados: A média, o desvio padrão e a variação da paquimetria foi: grupo I (n=38) 571 ±80 um, 408 a 784 um; grupo II (n=79) 598 ±80 um, 437 a 816 um; grupo III (n=30) 605 ±99 um, 454 a 945 um e grupo IV (n=8) 607 ±120 ?m, 410 a 781 ?m. Analisando o resultado da AV e a porcentagem de casos com espessura corneana acima de 651 um, foi observada associação linear significativa (P=0,037; ?2 de tendência linear) entre o aumento da paquimetria e a piora da AV. Analisando a associação entre os grupos de AV e a porcentagem de casos com espessura corneana abaixo da faixa de normalidade (<495 um), não foi encontrada significância estatística (P=0,92; x2 de Pearson). Quando analisado o resultado visual do grupo I em relação ao resultado dos grupos II+III+IV em conjunto, observou-se que somente 13% dos casos do grupo I e 30% dos casos dos demais grupos apresentaram espessura corneana maior do que 651 ?m. Essa correlação demonstrou significância estatística limítrofe (P=0,066; x2 de Pearson com correção de Yates). Conclusão: Observou-se associação linear significativa entre piora da AV corrigida e aumento da espessura corneana central. Quando analisados somente casos com paquimetria abaixo da faixa de normalidade, não foi observada associação significativa entre piora da AV corrigida e espessura corneana centralPurpose: To analyze the influence of central corneal thickness in the corrected visual acuity (VA) after deep lamellar endothelial corneal keratoplasty (DLEK). Methods: Retrospective study of 155 eyes of 127 patients 6 months post-op DLEK between March 2000 and March 2005. These patients had been previously diagnosed with either bullous keratopathy or Fuch\'s endothelial dystrophy. Patients with other ophthalmic conditions that could cause loss of vision were excluded. All patients underwent ophthalmic evaluation to determine corrected VA by means of refraction and central corneal thickness by means of ultrasonic pachymetry. Eyes were grouped according to visual acuity into 4 groups: I (20/20 - 20/30), II (20/40 - 20/50), III (20/60 - 20/80), IV (20/100 - 20/400). For statistical analysis and corelation with pachymetry, VA measurements were converted to logMAR. Categorical variables were created to express normal range corneal thickness status (from 495 to 651 um) using values published on the literature. Results: Mean and standart deviation pachymetry values were: group I (n=38) 571 ±80 ?m, ranging from 408 to 784 um; group II (n=79) 598 ±80 um, ranging from 437 to 816 ?m; group III (n=30) 605 ±99 um, ranging from 454 to 945 um and group IV (n=8) 607 ±120 um, ranging from 410 to 781 ?m. Analyzing the VA results and the percentage of cases with corneal thickness above 651 um, a significant linear correlation between higher pachymetry and worse VA was observed (P=0.037; linear trend). Analyzing the association between the different groups and the percentage of cases with corneal thickness bellow 495 um, there was no statistical significance (P=0.92; Pearson\'s x2). When analyzing the visual results of group I compared to groups II+III+IV together, it was observed that only 13% of group I cases and 30% of cases from the other groups presented corneal thickness greater then 651 um. This correlation showed borderline statistical significance (P=0.066; Pearson\'s x2 with Yates\' correction). Conclusions: A significant linear correlation between increased corneal thickness and worse VA was observed. When analyzing only cases bellow normal pachymetry, there was no correlation between corneal thickness and worse VA
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Jones, Christine. "A candidate gene based investigation of aberrant DNA methylation in the pathogenesis of primary cutaneous T-cell lymphoma." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/a-candidate-gene-based-investigation-of-aberrant-dna-methylation-in-the-pathogenesis-of-primary-cutaneous-tcell-lymphoma(dacab6e6-a162-4ac7-9cca-fd77cd3ae576).html.
Повний текст джерелаАнотація:
Primary cutaneous T-cell lymphoma (CTCL) is a clinically heterogeneous malignancy of mature skin-homing T-cells. Mycosis fungoides (MF) is an indo¬lent subtype of CTCL whilst Sezary syndrome (SS) is an aggressive leukaemic variant characterised by the presence of malignant Sezary cells in the periph¬eral blood. A role for epigenetic mechanisms in the pathogenesis of CTCL has been proposed but not extensively investigated. In this thesis, the contribution of DNA methylation to the regulation of SHP-1, Fas and PLS3, which have been implicated in the pathogenesis of CTCL, was examined. Gene expression was assessed on the mRNA and protein levels using qPCR and flow cytometry re¬spectively whilst DNA methylation was evaluated using bisulphite conversion and Pyrosequencing. Contrary to results in CTCL cell lines, primary malignant cells from CTCL patients did not display aberrant DNA methylation or dysregu-lated expression of SHP-1, a negative regulator of STATS signalling. Dysregula-tion of Fas, a key regulator of apoptosis, was observed in 34/47 SS patients with 13/47 showing over-expression compared to healthy controls and 21/47 showing under-expression, attributed to the positional hypermethylation of five CpG din-ucleotides in the Fas CpG island. PLS3, an actin-binding protein not normally expressed in any haematopoietic cell, was aberrantly expressed in malignant cells from 21/35 SS patients and 3/8 MF patients with demonstrated clonal blood in¬volvement. CpG dinucleotides 95-99 in the PLS3 CpG island were differentially methylated between healthy lymphocytes and keratinocytes, and hypomethyla-tion of these CpG dinucleotides was observed in SS patients expressing PLS3. To investigate expression of PLS3 on the protein level a novel anti-PLS3 anti¬body was raised and optimised for use in Western blotting, flow cytometry and immunofluorescence. In conclusion, these data demonstrate that SHP-1 is not regulated by methylation in primary CTCL cells whilst Fas is dysregulated by hypermethylation of five key CpG dinucleotides and PLS3 is dysregulated by hy-pomethylation of CpG dinucleotides 95-99.
Книги з теми "Tcell"
1
Tcell Lymphomas. Humana Press, 2012.
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2
Regulatory Tcells. Academic Press, 2011.
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3
B, Kemeron. Zhizn i tcel sobaki. Eksmo, 2015.
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4
Sekrety psihologicheskoj vojny. Tceli zadachi, metody, formy, opyt. Harvest, 1999.
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5
Trening vzaimodejstviya roditelej s det'mi. Tceli, zadachi i osnovnye printsipy. Rech', 2000.
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6
Culture, characterization, and cytotoxic activity of [gamma][delta] Tcells from patients with Ph(+) chronic myeloid leukemia: A potential role in cell therapy. Ottawa: National Library of Canada, 2002.
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7
Larkin, Ashling, Rebecca Horner, Zu Dominiak, and Catriona Laird. Pandemic Tales: Responses to Covid-19 and Lockdown. Edited by Chris Murray and Divya Jindal-Snape. University of Dundee, 2022. http://dx.doi.org/10.20933/100001241.
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Since 2016 the Scottish Centre for Comics Studies has produced a number of public information comics, many of them dealing with healthcare issues and science communication. This has been part of a research project looking into the educational potential of comics. We believe that comics, which combine words and images, engage readers in unique ways that can aid understanding. The medium is highly effective at communicating ideas clearly, but also provoking emotional, intellectual and imaginative responses. When the Coronavirus pandemic took hold in early 2020, sending the world into lockdown, we decided to create an anthology comic to help people reflect upon the impact of the virus. We wanted to capture the important transitions that everyone was making, and to tell the stories of the communities, groups, and individuals who were doing amazing things to help themselves and others. We sought to tell the stories of ordinary people in extraordinary circumstances. We also wanted to highlight the University of Dundee’s response. This has included scientists working to assist the global effort to find a vaccine, nursing students join the front line by completing their studies in practice, the creation of the Scrub Hub, which saw a partnership between the university, business and the public to create much needed PPE, creating guidance material and resources in partnership with British Psychological Society to support children and young people, school staff and families with educational and life transitions, and many other activities. In light of these inspiring tales of dedication and determination the comics team mobilised to help tell these stories in the best way we know how – through a comic! Pandemic Tales: Responses to Covid-19 and Lockdown collects stories about these strange and challenging times. During the pandemic and lockdown the stories created for this anthology were released individually as webcomics on the Scottish Centre for Comics Studies website and some through blogs published by the Transformative Change: Educational and Life Transitions (TCELT) Research Centre. These stories have now been collected here in one volume. Many thanks to all those who supported this project, from all the writers and artists creating the comics, to Professor John Rowan, Dr Clive Randall and Kaye Lister at the University of Dundee, who assisted with funding the project. We dedicate this comic to all those who we have lost to the pandemic, to everyone who has struggled through illness and the pressures of lockdown, and to all the scientists and healthcare workers around the world who have worked so hard to keep us safe. We are excited to share these stories with you, and there are many more to follow! Chris and Divya
Частини книг з теми "Tcell"
1
"TCell (Truss Cell Spar)." In Encyclopedia of Ocean Engineering, 1937. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-10-6946-8_300811.
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1
Torres Acosta, M. A., S. Weinberg, L. Morales-Nebreda, K. Helmin, A. M. Joudi, and B. D. Singer. "Regulatory TCell-Specific Loss of Adenosine Monophosphate Protein Kinase (AMPK) Impairs Suppressive Function and Potentiates Immune Response to B16 Melanoma Tumors." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1270.
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Garibaldi, Brian T., Franco D'Alessio, Clark Files, Jason Mock, Claudia Avalos, Eric Chau, Yoshiki Eto, Neil R. Aggarwal, Venkataramana Sidhaye, and Landon S. King. "Regulatory Tcells Reduce Fibroproliferation After LPS-Induced Lung Injury By Decreasing Fibrocyte Recruitment Through A CXCL12 Dependent Mechanism." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3508.
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Vatansever, Fatma, Masayoshi Kawakubo, Hoon Chung, and Michael R. Hamblin. "Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases." In SPIE BiOS, edited by Wei R. Chen. SPIE, 2013. http://dx.doi.org/10.1117/12.2001902.
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Araujo, Dejka, Sandra D'Angelo, George Demetri, Mihaela Druta, John Glod, Warren Chow, William Tap, et al. "Abstract A002: Autologous Tcells transduced with the affinity enhanced NY-ESO-1c259TCR in patients with synovial sarcoma expressing low levels of the NY-ESO-1 antigen." In Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/2326-6074.cricimteatiaacr18-a002.
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