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https://www.readbyqxmd.com/read/29666981/an-early-life-mucosal-insult-temporarily-decreases-acute-oxazolone-induced-inflammation-in-mice
#1
Katja M Bendtsen, Peter Tougaard, Axel K Hansen
Inflammatory priming of immune cells in early life may optimize the response to a subsequent inflammatory challenge later in life. To prime the immune cells in the gut in vivo through a short inflammatory insult, we administered a low dose of dextran sulfate sodium (DSS) to 5-weeks-old BALB/c mice in the drinking water. We hypothesized that DSS-primed mice would show decreased inflammation and difference in immunological profiling, when subjected to presensitizing and oxazolone-induced colitis by rectal instillation at 9 weeks compared to non-DSS-primed control mice...
April 18, 2018: Inflammation
https://www.readbyqxmd.com/read/29666412/extensive-t-cell-cross-reactivity-between-diverse-seasonal-influenza-strains-in-the-ferret-model
#2
Adrian J Reber, Nedzad Music, Jin Hyang Kim, Shane Gansebom, Jufu Chen, Ian York
Influenza virus causes widespread, yearly epidemics by accumulating surface protein mutations to escape neutralizing antibodies established from prior exposure. In contrast to antibody epitopes, T cell mediated immunity targets influenza epitopes that are more highly conserved and have potential for cross-protection. The extent of T cell cross-reactivity between a diverse array of contemporary and historical influenza strains was investigated in ferrets challenged with 2009 pandemic H1N1 influenza or the seasonal H3N2 strain, A/Perth/16/2009...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666307/interleukin-2-shapes-the-cytotoxic-t-cell-proteome-and-immune-environment-sensing-programs
#3
Christina M Rollings, Linda V Sinclair, Hugh J M Brady, Doreen A Cantrell, Sarah H Ross
Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to promote the differentiation of effector CD8+ cytotoxic T lymphocytes (CTLs). Using high-resolution mass spectrometry, we generated an in-depth characterization of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2 signaling through JAK1 and JAK3 (JAK1/3) increased the abundance of a key subset of proteins to induce the accumulation of critical cytokines and effector molecules in T cells...
April 17, 2018: Science Signaling
https://www.readbyqxmd.com/read/29666167/a-flexible-mhc-class-i-multimer-loading-system-for-large-scale-detection-of-antigen-specific-t-cells
#4
Jolien J Luimstra, Malgorzata A Garstka, Marthe C J Roex, Anke Redeker, George M C Janssen, Peter A van Veelen, Ramon Arens, J H Frederik Falkenburg, Jacques Neefjes, Huib Ovaa
Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#5
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29665919/-effect-and-clinical-significance-of-bortezomib-and-thalidomide-on-the-memory-t-cells-subsets-and-regulatory-t-cells-in-peripheral-blood-of-patients-with-multiple-myeloma
#6
Ling-Ling Shi, Han-Qing Li, Jian-Gang Mei, Xiao-Gang Zhou, Feng Li, Ping Song, Yong-Ping Zhai
OBJECTIVE: To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (Tm ) and regulatory T cells(Tregs) in patients with multiple myeloma(MM). METHODS: Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665000/increased-killer-b-cells-in-chronic-hcv-infection-may-lead-to-autoimmunity-and-increased-viral-load
#7
Nasren Eiza, Eli Zuckerman, Matthias Carlebach, Tova Rainis, Yair Goldberg, Zahava Vadasz
BACKGROUND: B regulatory (Breg) cells are characterized by various membrane markers, and the secretion of different inhibitory cytokines. A new subset of Breg cells was identified as CD5hi Fas-ligand (FasL)hi. Their main reported role is to suppress anti-viral and anti-tumor immune responses and hence, they have been dubbed "killer" B cells. In this study, we aim to assess the role of these cells in chronic hepatitis C virus (HCV) infection, and determine if they contribute to the increased viral load and persistence of HCV and its related autoimmunity...
April 17, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29664837/chronic-alcohol-ingestion-worsens-survival-and-alters-gut-epithelial-apoptosis-and-cd8-t-cell-function-after-pseudomonas-aeruginosa-pneumonia-induced-sepsis
#8
Nathan J Klingensmith, Katherine T Fay, John D Lyons, Ching-Wen Chen, Shunsuke Otani, Zhe Liang, Deena B Chihade, Eileen M Burd, Mandy L Ford, Craig M Coopersmith
Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis...
April 16, 2018: Shock
https://www.readbyqxmd.com/read/29664688/predictive-value-of-cd4-cd8-ratio-in-patients-with-breast-cancer-receiving-recombinant-human-thrombopoietin
#9
Junnan Xu, Lei Jiang, Hui Cao, Yufeng Jia, Shuo Wu, Cui Jiang, Tao Sun
Recombinant human thrombopoietin (rhTPO) is a key determinant of therapy for chemotherapy-induced thrombocytopenia (CIT) in patients with breast cancer. To assess the predictive value of preoperative inflammatory cells for response to rhTPO in breast cancer patients, a total of 198 female patients with breast cancer were enrolled between June 2011 and December 2016 in Liaoning Cancer Hospital. Peripheral blood samples before rhTPO therapy were obtained, the ratios of helper T cell (CD4+ ), cytotoxic T cell (CD8+ ), NK cell (CD16+ /CD56+ ), and B cell (CD19+ ) were analyzed, and CD4/CD8 ratios were calculated...
April 17, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29664577/the-gradual-rise-of-memory-inflation
#10
REVIEW
Paul Klenerman
Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T-cell population structure which maintains functionality and size...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664576/memory-vs-memory-like-the-different-facets-of-cd8-t-cell-memory-in-hcv-infection
#11
REVIEW
Maike Hofmann, Dominik Wieland, Hanspeter Pircher, Robert Thimme
Memory CD8+ T cells are essential in orchestrating protection from re-infection. Hallmarks of virus-specific memory CD8+ T cells are the capacity to mount recall responses with rapid induction of effector cell function and antigen-independent survival. Growing evidence reveals that even chronic infection does not preclude virus-specific CD8+ T-cell memory formation. However, whether this kind of CD8+ T-cell memory that is established during chronic infection is indeed functional and provides protection from re-infection is still unclear...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664573/tcr-repertoire-evolution-during-maintenance-of-cmv-specific-t-cell-populations
#12
REVIEW
Kilian Schober, Veit R Buchholz, Dirk H Busch
During infections and cancer, the composition of the T-cell receptor (TCR) repertoire of antigen-specific CD8+ T cells changes over time. TCR avidity is thought to be a major driver of this process, thereby interacting with several additional regulators of T-cell responses to form a composite immune response architecture. Infections with latent viruses, such as cytomegalovirus (CMV), can lead to large T-cell responses characterized by an oligoclonal TCR repertoire. Here, we review the current status of experimental studies and theoretical models of TCR repertoire evolution during CMV infection...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664571/tissue-resident-memory-t-cells-in-tissue-homeostasis-persistent-infection-and-cancer-surveillance
#13
REVIEW
Thomas Gebhardt, Umaimainthan Palendira, David C Tscharke, Sammy Bedoui
A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (TRM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of TRM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664569/fatty-acid-metabolism-in-cd8-t-cell-memory-challenging-current-concepts
#14
REVIEW
Brenda Raud, Peter J McGuire, Russell G Jones, Tim Sparwasser, Luciana Berod
CD8+ T cells are key members of the adaptive immune response against infections and cancer. As we discuss in this review, these cells can present diverse metabolic requirements, which have been intensely studied during the past few years. Our current understanding suggests that aerobic glycolysis is a hallmark of activated CD8+ T cells, while naive and memory (Tmem ) cells often rely on oxidative phosphorylation, and thus mitochondrial metabolism is a crucial determinant of CD8+ Tmem cell development. Moreover, it has been proposed that CD8+ Tmem cells have a specific requirement for the oxidation of long-chain fatty acids (LC-FAO), a process modulated in lymphocytes by the enzyme CPT1A...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664568/the-role-of-cytokines-in-t-cell-memory-in-health-and-disease
#15
REVIEW
Miro E Raeber, Yves Zurbuchen, Daniela Impellizzieri, Onur Boyman
Upon stimulation with their cognate antigen, naive T cells undergo proliferation and differentiation into effector cells, followed by apoptosis or survival as precursors of long-lived memory cells. These phases of a T-cell response and the ensuing maintenance of memory T cells are shaped by cytokines, most notably interleukin-2 (IL-2), IL-7, and IL-15 that share the common γ chain (γc ) cytokine receptor. Steady-state production of IL-7 and IL-15 is necessary for background proliferation and homeostatic survival of CD4+ and CD8+ memory T cells...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664565/memory-cd8-t-cell-inflation-vs-tissue-resident-memory-t-cells-same-patrollers-same-controllers
#16
REVIEW
Suzanne P M Welten, Ioana Sandu, Nicolas S Baumann, Annette Oxenius
The induction of long-lived populations of memory T cells residing in peripheral tissues is of considerable interest for T cell-based vaccines, as they can execute immediate effector functions and thus provide protection in case of pathogen encounter at mucosal and barrier sites. Cytomegalovirus (CMV)-based vaccines support the induction and accumulation of a large population of effector memory CD8 T cells in peripheral tissues, in a process called memory inflation. Tissue-resident memory (TRM ) T cells, induced by various infections and vaccination regimens, constitute another subset of memory cells that take long-term residence in peripheral tissues...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664561/the-function-and-dysfunction-of-memory-cd8-t-cells-in-tumor-immunity
#17
REVIEW
James L Reading, Felipe Gálvez-Cancino, Charles Swanton, Alvaro Lladser, Karl S Peggs, Sergio A Quezada
The generation and maintenance of CD8+ T cell memory is crucial to long-term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664020/accumulation-of-follicular-cd8-t-cells-in-pathogenic-siv-infection
#18
Sara Ferrando-Martinez, Eirini Moysi, Amarendra Pegu, Sarah Andrews, Krystelle Nganou Makamdop, David Ambrozak, Adrian B McDermott, David Palesch, Mirko Paiardini, George N Pavlakis, Jason M Brenchley, Daniel Douek, John R Mascola, Constantinos Petrovas, Richard A Koup
LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected cells from these areas. In this study, we provide a comprehensive analysis of the phenotype, frequency, localization, and functionality of follicular CD8+ T cells (fCD8+) in SIV-infected nonhuman primates. Although disorganization of follicles was a major factor, significant accumulation of fCD8+ cells during chronic SIV infection was also observed in intact follicles, but only in pathogenic SIV infection...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29664018/increased-vessel-perfusion-predicts-the-efficacy-of-immune-checkpoint-blockade
#19
Xichen Zheng, Zhaoxu Fang, Xiaomei Liu, Shengming Deng, Pei Zhou, Xuexiang Wang, Chenglin Zhang, Rongping Yin, Haitian Hu, Xiaolan Chen, Yijie Han, Yun Zhao, Steven H Lin, Songbing Qin, Xiaohua Wang, Betty Ys Kim, Penghui Zhou, Wen Jiang, Qingyu Wu, Yuhui Huang
Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663369/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#20
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
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