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https://www.readbyqxmd.com/read/29049397/the-transcriptional-regulator-lysg-rv1985c-of-mycobacterium-tuberculosis-activates-lyse-rv1986-in-a-lysine-dependent-manner
#1
Marie Schneefeld, Tobias Busche, Robert Geffers, Jörn Kalinowski, Franz-Christoph Bange
The Mycobacterium tuberculosis protein encoded by the Rv1986 gene is a target for memory T cells in patients with tuberculosis, and shows strong similarities to a lysine exporter LysE of Corynebacterium glutamicum. During infection, the pathogen Mycobacterium tuberculosis adapts its metabolism to environmental changes. In this study, we found that the expression of Rv1986 is controlled by Rv1985c. Rv1985c is located directly upstream of Rv1986 with an overlapping promoter region between both genes. Semiquantitative reverse transcription PCR using an isogenic mutant of Mycobacterium tuberculosis lacking Rv1985c showed that in the presence of lysine, Rv1985c protein positively upregulated the expression of Rv1986...
2017: PloS One
https://www.readbyqxmd.com/read/29049331/hiv-dynamics-linked-to-memory-cd4-t-cell-homeostasis
#2
John M Murray, John Zaunders, Sean Emery, David A Cooper, William J Hey-Nguyen, Kersten K Koelsch, Anthony D Kelleher
The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART...
2017: PloS One
https://www.readbyqxmd.com/read/29048671/adoptive-immunotherapy-combined-with-fp-treatment-for-head-and-neck-cancer-an-in%C3%A2-vitro-study
#3
Mayako Nishio-Nagai, Susumu Suzuki, Kazuhiro Yoshikawa, Ryuzo Ueda, Yoshiaki Kazaoka
FP treatment, which combines 5-fluorouracil (5-FU) and cisplatin (CDDP) chemotherapy, is widely used for treatment of advanced head and neck cancer (HNC). It has been suggested that these drugs cause immunomodulation in the cancer microenvironment, for example, downregulation of immunosuppressive cells such as regulatory T-cells (Tregs) and myeloid-derived suppressive cells (MDSCs), activating dendritic cells (DCs), and upregulation of tumor antigens and major histocompatibility complex (MHC) molecules in cancer cells leads to enhancement of cancer immunity, which is important in cancer treatment, as well as providing a direct killing effect...
October 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048429/different-death-destinies-relative-apoptosis-sensitivity-shapes-the-human-effector-cd8-t-cell-response-derived-from-distinct-memory-subsets
#4
Andrew L Snow, Sasha E Larsen
No abstract text is available yet for this article.
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29046675/interpreting-t-cell-cross-reactivity-through-structure-implications-for-tcr-based-cancer-immunotherapy
#5
Dinler A Antunes, Maurício M Rigo, Martiela V Freitas, Marcus F A Mendes, Marialva Sinigaglia, Gregory Lizée, Lydia E Kavraki, Liisa K Selin, Markus Cornberg, Gustavo F Vieira
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29045964/-increased-serum-c-c-chemokine-ligand-19-levels-correlated-with-b-cell-abnormalities-in-systemic-lupus-erythematosus
#6
H J Liu, L J Shi, F L Hu, H H Yao, Z G Li, Y Jia
OBJECTIVE: To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters, trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus. METHODS: The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29045906/ctla-4-pd-1-memory-cd4-t-cells-critically-contribute-to-viral-persistence-in-antiretroviral-therapy-suppressed-siv-infected-rhesus-macaques
#7
Colleen S McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D Estes, Rafick-Pierre Sekaly, Mirko Paiardini
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1(+) follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#8
Liang Shan, Kai Deng, Hongbo Gao, Sifei Xing, Adam A Capoferri, Christine M Durand, S Alireza Rabi, Gregory M Laird, Michelle Kim, Nina N Hosmane, Hung-Chih Yang, Hao Zhang, Joseph B Margolick, Linghua Li, Weiping Cai, Ruian Ke, Richard A Flavell, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting memory CD4(+) T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4(+) T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045899/early-transcriptional-divergence-marks-virus-specific-primary-human-cd8-t-cells-in-chronic-versus-acute-infection
#9
David Wolski, Peter K Foote, Diana Y Chen, Lia L Lewis-Ximenez, Catherine Fauvelle, Jasneet Aneja, Andreas Walker, Pierre Tonnerre, Almudena Torres-Cornejo, Daniel Kvistad, Sabrina Imam, Michael T Waring, Damien C Tully, Todd M Allen, Raymond T Chung, Jörg Timm, W Nicholas Haining, Arthur Y Kim, Thomas F Baumert, Georg M Lauer
Distinct molecular pathways govern the differentiation of CD8(+) effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8(+) T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4(+) T cell populations...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045893/hiv-1-latency-by-transition
#10
Boris Julg, Dan H Barouch
The latent HIV-1 reservoir represents the major barrier for the development of an HIV-1 cure. In this issue of Immunity, Shan et al. (2017) highlight that effector-to-memory transitioning (EMT) CD4(+) T cells are particularly permissive for the establishment of latent HIV-1 infection.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045846/identification-of-genetically-intact-hiv-1-proviruses-in-specific-cd4-t-cells-from-effectively-treated-participants
#11
Bonnie Hiener, Bethany A Horsburgh, John-Sebastian Eden, Kirston Barton, Timothy E Schlub, Eunok Lee, Susanne von Stockenstrom, Lina Odevall, Jeffrey M Milush, Teri Liegler, Elizabeth Sinclair, Rebecca Hoh, Eli A Boritz, Daniel Douek, Rémi Fromentin, Nicolas Chomont, Steven G Deeks, Frederick M Hecht, Sarah Palmer
Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4(+) T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045701/regulatory-t-cells-contribute-to-hiv-1-reservoir-persistence-in-cd4-t-cells-through-camp-dependent-mechanisms-in-humanized-mice-in-vivo
#12
Guangming Li, Jun-Ichi Nunoya, Liang Cheng, Natalia Reszka-Blanco, Li-Chung Tsao, Jerry Jeffrey, Lishan Su
Background: Regulatory T cells (Tregs) suppress T cell immune activation and HIV-1 replication, but the role of Tregs in HIV-1 reservoir persistence is poorly defined. Methods: Tregs were depleted in HIV-1 chronically infected humanized mice by Denileukin Diftitox. Viral replication in lineage cells was determined by p24 expression. HIV-1 RNA and DNA in human cells as well as replication-competent virus producing cells were measured to quantified viral replication and reservoirs...
October 14, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29045388/inflammatory-memory-sensitizes-skin-epithelial-stem-cells-to-tissue-damage
#13
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29043774/augmenting-influenza-specific-t-cell-memory-generation-with-a-nkt-cell-dependent-glycolipid-peptide-vaccine
#14
Regan J Anderson, Jasmine Li, Lukasz Kedzierski, Benjamin J Compton, Colin M Hayman, Taryn L Osmond, Ching-Wen Tang, Kathryn J Farrand, Hui-Fern Koay, Catarina Filipa Dos Santos Sa E Almeida, Lauren R Holz, Geoffrey M Williams, Margaret A Brimble, Zhongfang Wang, Marios Koutsakos, Katherine Kedzierska, Dale I Godfrey, Ian F Hermans, Stephen J Turner, Gavin F Painter
The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing health goal, particularly in the context of the increasing threat of new global pandemics. Vaccines that specifically induce T cell responses are of considerable interest because they can target viral proteins that are more like-ly to be shared between different virus strains and subtypes and hence provide effective cross-reactive IAV immunity. From a practical perspective, such vaccines should induce T cell responses with long-lasting memory, while also being simple to manufacture and cost-effective...
October 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29042482/resveratrol-stimulates-the-metabolic-reprogramming-of-human-cd4-t-cells-to-enhance-effector-function
#15
Marco Craveiro, Gaspard Cretenet, Cédric Mongellaz, Maria I Matias, Olivier Caron, Maria C Pedroso de Lima, Valérie S Zimmermann, Eric Solary, Valérie Dardalhon, Vjekoslav Dulić, Naomi Taylor
The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4(+) T cells showed defective antigen receptor signaling and arrest at the G1 stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia-mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest...
October 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/29042296/computations-in-the-deep-vs-superficial-layers-of-the-cerebral-cortex
#16
Edmund T Rolls, W Patrick C Mills
A fundamental question is how the cerebral neocortex operates functionally, computationally. The cerebral neocortex with its superficial and deep layers and highly developed recurrent collateral systems that provide a basis for memory-related processing might perform somewhat different computations in the superficial and deep layers. Here we take into account the quantitative connectivity within and between laminae. Using integrate-and-fire neuronal network simulations that incorporate this connectivity, we first show that attractor networks implemented in the deep layers that are activated by the superficial layers could be partly independent in that the deep layers might have a different time course, which might because of adaptation be more transient and useful for outputs from the neocortex...
October 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#17
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29038659/in-silico-prediction-analysis-of-idiotope-driven-t-b-cell-collaboration-in-multiple-sclerosis
#18
Rune A Høglund, Andreas Lossius, Jorunn N Johansen, Jane Homan, Jūratė Šaltytė Benth, Harlan Robins, Bjarne Bogen, Robert D Bremel, Trygve Holmøy
Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS), but the antigen they present remains unknown. We hypothesized that B cells may activate CD4(+) T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA) class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients and 6 controls with other inflammatory neurological disorders (OINDs), to assess whether the prerequisites for such idiotope-driven T-B cell collaboration are present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29038654/cpg-odn-facilitates-effective-intratracheal-immunization-and-recall-of-memory-against-neoantigen-expressing-alveolar-cells
#19
Mathias Riehn, Marcin Cebula, Hansjörg Hauser, Dagmar Wirth
Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA) exclusively in alveolar type II epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29035156/cd4-t-memory-stem-cells-correlate-with-disease-progression-in-chronically-hiv-1-infected-patients
#20
Xiaofan Lu, Bingbing Song, Wenjia Weng, Huan Xia, Bin Su, Hao Wu, Tong Zhang, Wei Li, Yanqing Gao
Recently identified T memory stem (Tscm) cells have stem-cell-like properties, including long lifespan, self-renewal capacity, and multipotency to differentiate into other memory T cell types. In the study of simian immunodeficiency virus (SIV) infection, selective depletion of CCR5(+)CD4(+) Tscm cells and the high proliferation rate of these cells are believed to be responsible for the pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study to investigate the influence of chronic human immunodeficiency virus (HIV)-1 infection on CD4(+) Tscm cell homeostasis, and the effect of antiretroviral therapy (ART) on CD4(+) Tscm cells...
October 16, 2017: Viral Immunology
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