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https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#1
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736203/oral-administration-of-visceral-adipose-tissue-antigens-ameliorates-metabolic-disorders-in-mice-and-elevates-visceral-adipose-tissue-resident-cd4-cd25-foxp3-regulatory-t-cells
#2
Xiangyu Chen, Dali Zhang, Xiaoling Chen, Gang Meng, Qian Zheng, Wenli Mai, Yuzhang Wu, Lilin Ye, Li Wang
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4(+)Foxp3(+) Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders...
July 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28736106/in-vivo-magnetic-resonance-approach-to-trimethyltin-induced-neurodegeneration-in-rats
#3
Ladislav Baciak, Zdenka Gasparova, Tibor Liptaj, Ivo Juranek
Trimethyltin (TMT) is commonly used to induce neurodegeneration in mice and rats; however, only scarce data of in vivo MR spectroscopy and imaging characterizing TMT neurotoxicity are available. Our aim was to assess brain metabolite changes and brain atrophy by in vivo MR in the rat model of neurodegeneration induced by TMT. Adult male Wistar rats exposed to TMT (8 mg/kg, i.p.) were used in the study. Proton MRS was applied on the dorsal hippocampus to reveal changes in neurochemical profile and MRI was used to assess the volume of the entire hippocampus, ventricles and whole brain...
July 20, 2017: Brain Research
https://www.readbyqxmd.com/read/28735895/a-phosphosite-within-the-sh2-domain-of-lck-regulates-its-activation-by-cd45
#4
Adam H Courtney, Jeanine F Amacher, Theresa A Kadlecek, Marianne N Mollenauer, Byron B Au-Yeung, John Kuriyan, Arthur Weiss
The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck...
July 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28733484/cutting-edge-cd3-itam-diversity-is-required-for-optimal-tcr-signaling-and-thymocyte-development
#5
Matthew L Bettini, Po-Chein Chou, Clifford S Guy, Thomas Lee, Kate M Vignali, Dario A A Vignali
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28733471/helicobacter-species-are-potent-drivers-of-colonic-t-cell-responses-in-homeostasis-and-inflammation
#6
Jiani N Chai, Yangqing Peng, Sunaina Rengarajan, Benjamin D Solomon, Teresa L Ai, Zeli Shen, Justin S A Perry, Kathryn A Knoop, Takeshi Tanoue, Seiko Narushima, Kenya Honda, Charles O Elson, Rodney D Newberry, Thaddeus S Stappenbeck, Andrew L Kau, Daniel A Peterson, James G Fox, Chyi-Song Hsieh
Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cell responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg cell responses during homeostasis and Teff cell responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733428/tcr-repertoire-intratumor-heterogeneity-in-localized-lung-adenocarcinomas-an-association-with-predicted-neoantigen-heterogeneity-and-postsurgical-recurrence
#7
Alexandre Reuben, Rachel M Gittelman, Jianjun Gao, Jiexin Zhang, Erik Yusko, Chang-Jiun Wu, Ryan Emerson, Jianhua Zhang, Christopher M Tipton, Jun Li, Kelly Quek, Vancheswaran Gopalakrishnan, Runzhe Chen, Luis Vence, Tina Cascone, Marissa Vignali, Junya Fujimoto, Jaime Rodriguez-Canales, Edwin R Parra, Latasha D Little, Curtis Gumbs, Marie-Andrée Forget, Lorenzo Federico, Cara Haymaker, Carmen Behrens, Sharon Benzeno, Chantale Bernatchez, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, William N William, Stephen G Swisher, John Heymach, Harlan Robins, J Jack Lee, Padmanee Sharma, James P Allison, P Andrew Futreal, Ignacio I Wistuba, Jianjun Zhang
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens were shown to alter tumor immunogenicity through T cell responses. Here, we performed sequencing of the T cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T cell density and clonality with the majority of T cell clones restricted to individual tumor regions...
July 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28731407/t-cell-receptor-repertoires-of-mice-and-humans-are-clustered-in-similarity-networks-around-conserved-public-cdr3-sequences
#8
Asaf Madi, Asaf Poran, Eric Shifrut, Shlomit Reich-Zeliger, Erez Greenstein, Irena Zaretsky, Tomer Arnon, Francois Van Laethem, Alfred Singer, Jinghua Lu, Peter D Sun, Irun R Cohen, Nir Friedman
Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-tregs-prevent-gvhd-while-allowing-a-powerful-t-cell-dependent-gvl-effect-in-murine-models
#9
B Del Papa, L Ruggeri, E Urbani, S Baldoni, D Cecchini, T Zei, R Iacucci Ostini, B Crescenzi, A Carotti, A Pierini, P Sportoletti, P Di Bartolomeo, F Falzetti, C Mecucci, A Velardi, M F Martelli, M Di Ianni
We developed a GMP-compatible expansion protocol, to improve number and purity of Tregs available for clinical trials. Six clinical grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation and rapamycin for 19 days achieving a median of 8.5 fold (6.25-13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong MLR inhibition...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28728750/trigeminocardiac-reflex-during-non-surgical-root-canal-treatment-of-teeth-with-irreversible-pulpitis
#10
James I-Sheng Huang, Hao-Hueng Chang, Chun-Pei Lin, Wan-Chuen Liao, Chia-Tze Kao, Tsui-Hsien Huang
BACKGROUND/PURPOSE: Trigeminocardiac reflex (TCR) is a unique clinical incident of acute change in hemodynamic balance, which may lead to hypotension, bradycardia, and even clinical crisis. Up to date, no study so far considers the impact of non-surgical root canal treatment (NSRCT) of irreversible pulpitis teeth under either local infiltration or block anesthesia on hemodynamic change possibly related to TCR. METHODS: This study enrolled 111 patients with 138 irreversible pulpitis teeth that were treated by two sessions of NSRCT...
July 17, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#11
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28725432/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#12
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#13
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#14
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28723478/low-t-cell-receptor-diversity-high-somatic-mutation-burden-and-high-neoantigen-load-as-predictors-of-clinical-outcome-in-muscle-invasive-bladder-cancer
#15
Noura J Choudhury, Kazuma Kiyotani, Kai Lee Yap, Alexa Campanile, Tatjana Antic, Poh Yin Yew, Gary Steinberg, Jae Hyun Park, Yusuke Nakamura, Peter H O'Donnell
BACKGROUND: The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. OBJECTIVE: To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723412/identification-of-a-viroid-like-rna-in-a-lychee-transcriptome-shotgun-assembly
#16
Jihong Jiang, Zhixiang Zhang, Bing Hu, Guibing Hu, Hongqing Wang, Chantal Faure, Armelle Marais, Thierry Candresse, Shifang Li
In the course of a systematic screen of plant transcriptomic data, the sequence of a novel viroid-like RNA was identified in four contigs in a recent Transcriptome Shotgun Assembly (TSA) from lychee in China. Portions of this sequence are closely related to the central conserved region (CCR) and terminal conserved region (TCR) present in members of the genus Apscaviroid, sequences that are important criteria for viroid classification. RT-PCR with two divergent adjacent primers amplified the full 304 nucleotide sequence of this viroid-like RNA which can be folded into the rod-like secondary structure that is a typical feature of viroids in the family Pospiviroidae...
July 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28716901/structural-determination-of-lipid-antigens-captured-at-the-cd1d-t-cell-receptor-interface
#17
Patrick J Brennan, Tan-Yun Cheng, Daniel G Pellicci, Gerald F M Watts, Natacha Veerapen, David C Young, Jamie Rossjohn, Gurdyal S Besra, Dale I Godfrey, Michael B Brenner, D Branch Moody
Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a "foreign" lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716889/cytokines-transcription-factors-and-the-initiation-of-t-cell-development
#18
Hiroyuki Hosokawa, Ellen V Rothenberg
Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716155/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#19
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28714979/translation-is-actively-regulated-during-the-differentiation-of-cd8-effector-t-cells
#20
Koichi Araki, Masahiro Morita, Annelise G Bederman, Bogumila T Konieczny, Haydn T Kissick, Nahum Sonenberg, Rafi Ahmed
Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8(+) effector T cells (Teff cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8(+) Teff cells stopped dividing just before the contraction phase...
July 17, 2017: Nature Immunology
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