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https://www.readbyqxmd.com/read/29348660/generation-and-characterization-of-alloantigen-specific-regulatory-t-cells-for-clinical-transplant-tolerance
#1
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#2
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#3
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344432/wt1-peptide-vaccine-in-montanide-in-contrast-to-poly-iclc-is-able-to-induce-wt1-specific-immune-response-with-tcr-clonal-enrichment-in-myeloid-leukemia
#4
Hongtao Liu, Yuanyuan Zha, Noura Choudhury, Gregory Malnassy, Noreen Fulton, Margaret Green, Jae-Hyun Park, Yusuke Nakamura, Richard A Larson, Andres M Salazar, Olatoyosi Odenike, Thomas F Gajewski, Wendy Stock
Background: The optimal strategy for vaccination to induce CD8+ T cell responses against WT1 is not known. Methods: A pilot randomized study in HLA-A02+ patients to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to explore the novel immune adjuvant was conducted. Seven patients were randomized. Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five patients were in morphologic remission and two had residual morphologic disease at the study entry...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29343684/mait-cell-clonal-expansion-and-tcr-repertoire-shaping-in-human-volunteers-challenged-with-salmonella-paratyphi%C3%A2-a
#5
Lauren J Howson, Giorgio Napolitani, Dawn Shepherd, Hemza Ghadbane, Prathiba Kurupati, Lorena Preciado-Llanes, Margarida Rei, Hazel C Dobinson, Malick M Gibani, Karen Wei Weng Teng, Evan W Newell, Natacha Veerapen, Gurdyal S Besra, Andrew J Pollard, Vincenzo Cerundolo
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339503/heteromeric-interactions-regulate-butyrophilin-btn-and-btn-like-molecules-governing-%C3%AE-%C3%AE-t-cell-biology
#6
Pierre Vantourout, Adam Laing, Martin J Woodward, Iva Zlatareva, Luis Apolonia, Andrew W Jones, Ambrosius P Snijders, Michael H Malim, Adrian C Hayday
The long-held view that gamma delta (γδ) T cells in mice and humans are fundamentally dissimilar, as are γδ cells in blood and peripheral tissues, has been challenged by emerging evidence of the cells' regulation by butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of murine intraepithelial γδ T cell repertoires in gut and skin, respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut γδ cells; and BTN3A1 is essential for TCR-dependent activation of human peripheral blood Vγ9Vδ2+ T cells...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#7
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29337047/imaging-flow-cytometry-a-method-for-examining-dynamic-native-foxo1-localization-in-human-lymphocytes
#8
Molly K Hritzo, Jean-Paul Courneya, Amit Golding
While flow cytometry can reliably assess surface and intracellular marker expression within small cell populations, it does not provide any information on protein localization. Several key transcription factors (TF) downstream of lymphocyte surface receptors are regulated by nuclear versus cytoplasmic localization, and one such TF is Forkhead box O1 (FOXO1). FOXO1 integrates antigen-binding, co-receptor activation and metabolic signals in lymphocytes, leading to proliferation and differentiation. Importantly, the nuclear or cytoplasmic localization of FOXO1 is key for gene expression leading to different lymphocyte phenotypes...
January 11, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29335257/staphylococcal-superantigens-use-lama2-as-a-coreceptor-to-activate-t-cells
#9
Zhigang Li, Joseph J Zeppa, Mark A Hancock, John K McCormick, Terence M Doherty, Geoffrey N Hendy, Joaquín Madrenas
Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein-coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29334915/monitoring-the-responsiveness-of-t-and-antigen-presenting-cell-compartments-in-breast-cancer-patients-is-useful-to-predict-clinical-tumor-response-to-neoadjuvant-chemotherapy
#10
David A Bernal-Estévez, Oscar García, Ramiro Sánchez, Carlos A Parra-López
BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. METHODS: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C...
January 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29333753/comparative-performance-of-different-scale-down-simulators-of-substrate-gradients-in-penicillium-chrysogenum-cultures-the-need-of-a-biological-systems-response-analysis
#11
Guan Wang, Junfei Zhao, Cees Haringa, Wenjun Tang, Jianye Xia, Ju Chu, Yingping Zhuang, Siliang Zhang, Amit T Deshmukh, Walter van Gulik, Joseph J Heijnen, Henk J Noorman
In a 54 m3 large-scale penicillin fermentor, the cells experience substrate gradient cycles at the timescales of global mixing time about 20-40 s. Here, we used an intermittent feeding regime (IFR) and a two-compartment reactor (TCR) to mimic these substrate gradients at laboratory-scale continuous cultures. The IFR was applied to simulate substrate dynamics experienced by the cells at full scale at timescales of tens of seconds to minutes (30 s, 3 min and 6 min), while the TCR was designed to simulate substrate gradients at an applied mean residence time (τc) of 6 min...
January 15, 2018: Microbial Biotechnology
https://www.readbyqxmd.com/read/29330323/il-10-deficiency-reveals-a-role-for-tlr2-dependent-bystander-activation-of-t-cells-in-lyme-arthritis
#12
Sarah K Whiteside, Jeremy P Snook, Ying Ma, F Lynn Sonderegger, Colleen Fisher, Charisse Petersen, James F Zachary, June L Round, Matthew A Williams, Janis J Weis
T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non-Borrelia epitopes confirmed that bystander T cell activation was responsible for disease development...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330322/cutting-edge-piezo1-mechanosensors-optimize-human-t-cell-activation
#13
Chinky Shiu Chen Liu, Deblina Raychaudhuri, Barnali Paul, Yogaditya Chakrabarty, Amrit Raj Ghosh, Oindrila Rahaman, Arindam Talukdar, Dipyaman Ganguly
TCRs recognize peptides on MHC molecules and induce downstream signaling, leading to activation and clonal expansion. In addition to the strength of the interaction of TCRs with peptides on MHC molecules, mechanical forces contribute to optimal T cell activation, as reflected by the superior efficiency of immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering, although a dedicated mechanotransduction module is not identified. We found that the professional mechanosensor protein Piezo1 is critically involved in human T cell activation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29316940/gamma-delta-%C3%AE-%C3%AE-t-cells-friend-or-foe-in-cancer-development
#14
REVIEW
Yijing Zhao, Chao Niu, Jiuwei Cui
BACKGROUND: γδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems, γδ T cells participate in various immune responses during cancer progression. Because of their direct/indirect antitumor cytotoxicity and strong cytokine production ability, the use of γδ T cells in cancer immunotherapy has received a lot of attention over the past decade...
January 10, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29315518/hyaluronan-binding-by-cd44-reduces-the-memory-potential-of-activated-murine-cd8-t-cells
#15
Sally S M Lee-Sayer, Nina Maeshima, Meghan N Dougan, Anita Dahiya, Arif A Arif, Manisha Dosanjh, Christopher A Maxwell, Pauline Johnson
Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site...
January 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29305709/influence-of-physical-activity-on-the-immune-system-in-breast-cancer-patients-during-chemotherapy
#16
Thorsten Schmidt, Walter Jonat, Daniela Wesch, Hans-Heinrich Oberg, Sabine Adam-Klages, Lisa Keller, Christoph Röcken, Christoph Mundhenke
PURPOSE: Physical activity can impact the immune system in different ways, e.g. by alteration of the humoral and cellular immune response. Physical activity at medium intensity enhances numbers of cytotoxic T cells, NK cells and macrophages in healthy people. The aim of this study was to compare the effects of endurance and resistance training on the immune system in breast cancer patients during adjuvant chemotherapy. METHODS: In a prospective, controlled and randomized intervention exploratory trial, 12-week supervised endurance or resistance training were compared with usual care twice a week...
January 5, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29305140/innate-like-cytotoxic-function-of-bystander-activated-cd8-t-cells-is-associated-with-liver-injury-in-acute-hepatitis-a
#17
Jihye Kim, Dong-Yeop Chang, Hyun Woong Lee, Hoyoung Lee, Jong Hoon Kim, Pil Soo Sung, Kyung Hwan Kim, Seon-Hui Hong, Wonseok Kang, Jino Lee, So Youn Shin, Hee Tae Yu, Sooseong You, Yoon Seok Choi, Insoo Oh, Dong Ho Lee, Dong Hyeon Lee, Min Kyung Jung, Kyung-Suk Suh, Shin Hwang, Won Kim, Su-Hyung Park, Hyung Joon Kim, Eui-Cheol Shin
Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement...
December 30, 2017: Immunity
https://www.readbyqxmd.com/read/29305065/high-macrophage-pd-l1-expression-not-responsible-for-t-cell-suppression
#18
Naomi Goldman, Yelizavet D Lomakova, Jennifer Londregan, Amanda Bucknum, Kelley DePierri, John Somerville, James E Riggs
Tumors are often comprised of microenvironments (TMEs) with a high proportion of cells and molecules that regulate immunity. Peritoneal cavity (PerC) cell culture reproduces key features of TMEs as lymphocyte proliferation is suppressed by PerC macrophages (Mϕs). We monitored the expression of T cell stimulatory (Class II MHC, B7) and inhibitory (PD-L1) molecules by PerC APCs before and after culture and report here that IFNγ-driven PD-L1 expression increased markedly on PerC Mϕs after TCR ligation, even more so than seen with direct APC activation by LPS...
December 30, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29301753/exosomes-associated-with-human-ovarian-tumors-harbor-a-reversible-checkpoint-of-t-cell-responses
#19
Gautam N Shenoy, Jenni L Loyall, Orla Maguire, Vandana Iyer, Raymond J Kelleher, Hans Minderman, Paul K Wallace, Kunle Odunsi, Sathy V Balu-Iyer, Richard B Bankert
Nano-sized membrane-encapsulated extracellular vesicles isolated from the ascites fluids of ovarian cancer patients are identified as exosomes based on their biophysical and compositional characteristics. We report here that T cells pulsed with these tumor-associated exosomes during TCR-dependent activation inhibit various activation endpoints including translocation of NFkB and NFAT into the nucleus, upregulation of CD69 and CD107a, production of cytokines and cell proliferation. Additionally, the activation of virus-specific CD8+ T cells that are stimulated with the cognate viral peptides presented in the context of class I MHC is also suppressed by the exosomes...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29298833/production-of-il-17-by-mait-cells-is-increased-in-multiple-sclerosis-and-is-associated-with-il-7-receptor-expression
#20
Anne Willing, Jan Jäger, Stefanie Reinhardt, Nina Kursawe, Manuel A Friese
Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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