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https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#1
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#2
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#3
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#4
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769260/bim-regulates-the-survival-and-suppressive-capability-of-cd8-foxp3-regulatory-t-cells-during-murine-gvhd
#5
Kimberle Agle, Benjamin G Vincent, Clint Piper, Ludovic Belle, Vivian Zhou, Warren Shlomchik, Jonathan S Serody, William R Drobyski
CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft versus host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppression of GVHD. To define the mechanistic basis for this observation, we examined the T cell repertoire and the transcriptional profile of in vivo-derived CD4+ and CD8+ Tregs that emerged early during this disease...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29765548/transformation-of-mouse-t-cells-requires-myc-and-akt-activity-in-conjunction-with-inhibition-of-intrinsic-apoptosis
#6
Kari Högstrand, Stephanie Darmanin, TachaZi Plym Forshell, Alf Grandien
Peripheral T-cell lymphoma is an aggressive non-Hodgkin's lymphoma characterized by excessive proliferation of transformed mature T cells. The number and nature of genetic aberrations required and sufficient for transformation of normal T cells into lymphomas is unknown. Here, using a combinatorial in vitro -approach, we demonstrate that overexpression of MYC together with activated AKT in conditions of inhibition of intrinsic apoptosis rapidly resulted in transformation of mature mouse T cells with a frequency approaching 100%...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763678/acute-aerobic-exercise-induces-a-preferential-mobilisation-of-plasmacytoid-dendritic-cells-into-the-peripheral-blood-in-man
#7
Frankie F Brown, John P Campbell, Alex J Wadley, James P Fisher, Sarah Aldred, James E Turner
Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise...
May 12, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29762692/overarching-immunodominance-patterns-and-substantial-diversity-in-specificity-and-functionality-in-the-circulating-human-influenza-a-and-b-cd4-t-cell-repertoire
#8
Katherine A Richards, John J Treanor, Jennifer L Nayak, Andrea J Sant
There is limited information on the antigen specificity and functional potential of the influenza-specific CD4 T cell repertoire in humans. Here, ELISPOT assays were used to examine circulating CD4 T cell influenza specificities directly ex vivo in healthy adults.  Our studies revealed CD4 T cell reactivity to multiple influenza proteins, including hemagglutinins, NA, M1 and NP. Unexpectedly, the immunodominance hierarchies and functional potential of cells reactive toward influenza A were distinct from influenza B...
May 12, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29760713/human-leukocyte-antigen-class-i-alleles-and-the-autoreactive-t-cell-response-in-psoriasis-pathogenesis
#9
REVIEW
Jörg Christoph Prinz
Psoriasis is a complex immune-mediated inflammatory skin disease characterized by T-cell-driven epidermal hyperplasia. It occurs on a strong genetic predisposition. The human leukocyte antigen (HLA)-class I allele HLA-C*06:02 on psoriasis susceptibility locus 1 (PSORS1 on 6p21.3) is the main psoriasis risk gene. Other HLA-class I alleles encoding HLA molecules presenting overlapping peptide repertoires show associations with psoriasis as well. Outside the major histocompatibility complex region, genome-wide association studies identified more than 60 psoriasis-associated common gene variants exerting only modest individual effects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29757191/disease-driving-cd4-t-cell-clonotypes-persist-for-decades-in-celiac-disease
#10
Louise F Risnes, Asbjørn Christophersen, Shiva Dahal-Koirala, Ralf S Neumann, Geir K Sandve, Vikas K Sarna, Knut Ea Lundin, Shuo-Wang Qiao, Ludvig M Sollid
Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29755475/impact-of-a-3-months-vegetarian-diet-on-the-gut-microbiota-and-immune-repertoire
#11
Chenchen Zhang, Andrea Björkman, Kaiye Cai, Guilin Liu, Chunlin Wang, Yin Li, Huihua Xia, Lijun Sun, Karsten Kristiansen, Jun Wang, Jian Han, Lennart Hammarström, Qiang Pan-Hammarström
The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753885/immunological-responses-to-influenza-vaccination-lessons-for-improving-vaccine-efficacy
#12
REVIEW
Taia T Wang, Stylianos Bournazos, Jeffrey V Ravetch
A critical factor in the maturation of influenza vaccine responses is the nearly inevitable binding of vaccine antigens by exiting anti-influenza IgGs. These antigen-IgG immune complexes direct the response to immunization by modulating cellular processes that determine antibody and T-cell repertoires: maturation of dendritic cells, processing and presentation of antigens to T cells, trafficking of antigens to the germinal center, and selection of B cells for antibody production. By focusing on the recent advances in the study of the immunomodulatory processes mediated by IgG immune complexes upon influenza vaccination, we discuss a pathway that is critical for modulating the breadth and potency of anti-HA antibody responses and has previously led to the development of strategies to improve influenza vaccine efficacy...
May 10, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29753741/long-term-hindlimb-unloading-causes-a-preferential-reduction-of-medullary-thymic-epithelial-cells-expressing-autoimmune-regulator-aire
#13
Kenta Horie, Takashi Kudo, Riko Yoshinaga, Nobuko Akiyama, Hiroki Sasanuma, Tetsuya J Kobayashi, Miki Shimbo, Hyojung Jeon, Takahisa Miyao, Maki Miyauchi, Masaki Shirakawa, Dai Shiba, Nobuaki Yoshida, Masafumi Muratani, Satoru Takahashi, Taishin Akiyama
Hindlimb unloading (HU) of rodents has been used as a ground-based model of spaceflight. In this study, we investigated the detailed impact of 14-day HU on the murine thymus. Thymic mass and cell number were significantly reduced after 14 days of hindlimb unloading, which was accompanied by an increment of plasma corticosterone. Although corticosterone reportedly causes selective apoptosis of CD4+ CD8+ thymocytes (CD4+ CD8+ DPs) in mice treated with short-term HU, the reduction of thymocyte cellularity after the 14-day HU was not selective for CD4+ CD8+ DPs...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752423/strong-homeostatic-tcr-signals-induce-formation-of-self-tolerant-virtual-memory-cd8-t-cells
#14
Ales Drobek, Alena Moudra, Daniel Mueller, Martina Huranova, Veronika Horkova, Michaela Pribikova, Robert Ivanek, Susanne Oberle, Dietmar Zehn, Kathy D McCoy, Peter Draber, Ondrej Stepanek
Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8+ T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells...
May 11, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29752065/cd36-mediates-cell-surface-antigens-to-promote-thymic-development-of-the-regulatory-t-cell-receptor-repertoire-and-allo-tolerance
#15
Justin S A Perry, Emilie V Russler-Germain, You W Zhou, Whitney Purtha, Matthew L Cooper, Jaebok Choi, Mark A Schroeder, Vanessa Salazar, Takeshi Egawa, Byeong-Chel Lee, Nada A Abumrad, Brian S Kim, Mark S Anderson, John F DiPersio, Chyi-Song Hsieh
The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens...
April 30, 2018: Immunity
https://www.readbyqxmd.com/read/29748647/isolation-and-functional-assessment-of-mouse-skeletal-stem-cell-lineage
#16
Gunsagar S Gulati, Matthew P Murphy, Owen Marecic, Michael Lopez, Rachel E Brewer, Lauren S Koepke, Anoop Manjunath, Ryan C Ransom, Ankit Salhotra, Irving L Weissman, Michael T Longaker, Charles K F Chan
There are limited methods available to study skeletal stem, progenitor, and progeny cell activity in normal and diseased contexts. Most protocols for skeletal stem cell isolation are based on the extent to which cells adhere to plastic or whether they express a limited repertoire of surface markers. Here, we describe a flow cytometry-based approach that does not require in vitro selection and that uses eight surface markers to distinguish and isolate mouse skeletal stem cells (mSSCs); bone, cartilage, and stromal progenitors (mBCSPs); and five downstream differentiated subtypes, including chondroprogenitors, two types of osteoprogenitors, and two types of hematopoiesis-supportive stroma...
June 2018: Nature Protocols
https://www.readbyqxmd.com/read/29743973/apoptosis-and-mobilization-of-lymphocytes-to-cardiac-tissue-is-associated-with-myocardial-infarction-in-a-reperfused-porcine-model-and-infarct-size-in-post-pci-patients
#17
Maria J Forteza, Isabel Trapero, Arantxa Hervas, Elena de Dios, Amparo Ruiz-Sauri, Gema Minana, Clara Bonanad, Cristina Gómez, Ricardo Oltra, Cesar Rios-Navarro, Daniel F J Ketelhuth, Julio Nunez, Francisco J Chorro, Vicente Bodi
ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743177/hypomorphic-rag1-mutations-alter-the-pre-immune-repertoire-at-early-stages-of-lymphoid-development
#18
Lisa M Ott de Bruin, Marita Bosticardo, Alessandro Barbieri, Sherry G Lin, Jared H Rowe, Pietro L Poliani, Kimberly Ching, Daniel Eriksson, Nils Landegren, Olle Kämpe, John P Manis, Luigi D Notarangelo
Hypomorphic RAG1 mutations allowing residual T and B cell development have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI) and abnormalities of the peripheral T and B cell repertoire. To examine how hypomorphic Rag1 mutations affect the earliest stages of lymphocyte development, we used CRISPR/Cas9 to generate mouse models with equivalent mutations found in patients with CID-G/AI. Immunological characterization showed partial development of T and B lymphocytes, with persistence of naïve cells, preserved serum immunoglobulin, but impaired antibody responses and presence of autoantibodies, thereby recapitulating the phenotype seen in patients with CID-G/AI...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29740455/sequence-based-discovery-demonstrates-that-fixed-light-chain-human-transgenic-rats-produce-a-diverse-repertoire-of-antigen-specific-antibodies
#19
Katherine E Harris, Shelley Force Aldred, Laura M Davison, Heather Anne N Ogana, Andrew Boudreau, Marianne Brüggemann, Michael Osborn, Biao Ma, Benjamin Buelow, Starlynn C Clarke, Kevin H Dang, Suhasini Iyer, Brett Jorgensen, Duy T Pham, Payal P Pratap, Udaya S Rangaswamy, Ute Schellenberger, Wim C van Schooten, Harshad S Ugamraj, Omid Vafa, Roland Buelow, Nathan D Trinklein
We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29735644/invariant-nkt-cells-and-control-of-the-thymus-medulla
#20
REVIEW
Andrea J White, Beth Lucas, William E Jenkinson, Graham Anderson
Most αβ T cells that form in the thymus are generated during mainstream conventional thymocyte development and involve the generation and selection of a diverse αβ TCR repertoire that recognizes self-peptide/MHC complexes. Additionally, the thymus also supports the production of T cell subsets that express αβ TCRs but display unique developmental and functional features distinct from conventional αβ T cells. These include multiple lineages of CD1d-restricted invariant NKT (iNKT) cells that express an invariant αβ TCR, branch off from mainstream thymocytes at the CD4+ CD8+ stage, and are potent producers of polarizing cytokines...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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