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T cell exhaustion

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https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#1
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28529635/synthesis-of-5-18-f-fluoro-%C3%AE-methyl-tryptophan-new-trp-based-pet-agents
#2
Benjamin C Giglio, Haiyang Fei, Mengzhe Wang, Hui Wang, Liu He, Huijuan Feng, Zhanhong Wu, Hongjian Lu, Zibo Li
Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of (18)F into the tryptophan aromatic ring...
2017: Theranostics
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#3
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28522830/inhibition-of-endocytic-lipid-antigen-presentation-by-common-lipophilic-environmental-pollutants
#4
Manju Sharma, Xiang Zhang, Shuangmin Zhang, Liang Niu, Shuk-Mei Ho, Aimin Chen, Shouxiong Huang
Environmental pollutants as non-heritable factors are now recognized as triggers for multiple human inflammatory diseases involving T cells. We postulated that lipid antigen presentation mediated by cluster of differentiation 1 (CD1) proteins for T cell activation is susceptible to lipophilic environmental pollutants. To test this notion, we determined whether the common lipophilic pollutants benzo[a]pyrene and diesel exhaust particles impact on the activation of lipid-specific T cells. Our results demonstrated that the expression of CD1a and CD1d proteins, and the activation of CD1a- and CD1d-restricted T cells were sensitively inhibited by benzo[a]pyrene even at the low concentrations detectable in exposed human populations...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#5
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28492391/hepatitis-c-virus-drives-increased-type-i-interferon-associated-impairments-associated-with-fibrosis-severity-in-antiretroviral-treatment-treated-hiv-1-hepatitis-c-virus-coinfected-individuals
#6
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28490589/roles-of-m1-and-m2-macrophages-in-herpes-simplex-virus-1-infectivity
#7
Dhong Hyun Lee, Homayon Ghiasi
Macrophages are the predominant infiltrate in the corneas of mice that have been ocularly infected withHSV-1. However, very little is known concerning the relative roles of M1 (classically activated or polarized) and M2 (alternatively activated or polarized) macrophages in ocular HSV-1 infection. To better understand these relationships, we assessed the impact of directed M1 or M2 activation of RAW264.7 macrophages and peritoneal macrophages (PM) on subsequent HSV-1 infection. In both the RAW264.7 macrophage and PM in vitro models, HSV-1 replication in M1 macrophages was markedly lower than in M2 macrophages and unstimulated controls...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28488141/elevated-t-cell-activation-score-is-associated-with-improved-survival-of-breast-cancer
#8
Lingeng Lu, Yalai Bai, Zuoheng Wang
PURPOSE: Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8(+) T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer. METHODS: Using a publicly accessed RNA-seq dataset including 1087 breast cancer patients, we performed Kaplan-Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients' overall survival...
May 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28482391/-two-families-of-x-linked-lymphoproliferative-disease-type-1-characterized-by-agammaglobulinemia
#9
W Y Li, J S Chen, Q Zhao, R X Dai, Y P Wang, H Y Zhao, X M Chen, X H Xue, X Y Sun, X M Tang, Y Zhang, Y Ding, X D Zhao, Z Y Zhang
Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry...
May 4, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28482051/biomarkers-of-chronic-acrolein-inhalation-exposure-in-mice-implications-for-tobacco-product-induced-toxicity
#10
Daniel J Conklin, Marina V Malovichko, Iris Zeller, Trinath P Das, Tatiana V Krivokhizhina, Blake H Lynch, Pawel Lorkiewicz, Abhinav Agarwal, Nalinie Wickramasinghe, Petra Haberzettl, Srinivas D Sithu, Jasmit Shah, Timothy E O'Toole, Shesh N Rai, Aruni Bhatnagar, Sanjay Srivastava
Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28478837/the-spread-of-ebv-to-ectopic-lymphoid-aggregates-may-be-the-final-common-pathway-in-the-pathogenesis-of-me-cfs
#11
Willy Eriksen
According to the hypothesis presented here, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops over 3 steps: Step 1 is characterized by the aggregation of lymphoid cells in dorsal root ganglia or other nervous structures. The cause of this formation of ectopic lymphoid aggregates may be an acute infection, asymptomatic reactivations of a common neurotropic virus, exposure to a neurotoxin, or physical injury to peripheral nerves. In step 2, Epstein-Barr virus (EBV)-infected lymphocytes or monocytes bring EBV from the circulation to one or several of these lymphoid aggregates, whereupon cell-to-cell transmission of EBV and proliferation of latently EBV-infected lymphocytes lead to the presence of many EBV-infected cells in the lymphoid aggregates...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28475007/tim-3-plays-a-more-important-role-than-pd-1-in-the-functional-impairments-of-cytotoxic-t-cells-of-malignant-schwannomas
#12
Zhao Li, Xiaobing Liu, Rongbin Guo, Pengfei Wang
Cancer immunotherapy using cytotoxic T cells demonstrates dramatic survival benefits in lymphomas, but its efficacy in solid tumors is limited. Here, we investigated the possibility of using cytotoxic T cells to treat malignant Schwannoma, a rare but aggressive nerve sheath tumor, by examining the native T-cell immunity in the host. We found that compared to CD8(+) T cells from healthy controls or benign Schwannoma patients, the CD8(+) T cells from malignant Schwannoma patients were present at normal frequencies but were substantially enriched with PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) cells...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28474673/single-cell-rna-seq-enables-comprehensive-tumour-and-immune-cell-profiling-in-primary-breast-cancer
#13
Woosung Chung, Hye Hyeon Eum, Hae-Ock Lee, Kyung-Min Lee, Han-Byoel Lee, Kyu-Tae Kim, Han Suk Ryu, Sangmin Kim, Jeong Eon Lee, Yeon Hee Park, Zhengyan Kan, Wonshik Han, Woong-Yang Park
Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways...
May 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28468877/preservation-of-peripheral-t-follicular-helper-cell-function-in-hiv-controllers
#14
Supranee Buranapraditkun, Franco Pissani, Jeffrey E Teigler, Bruce T Schultz, Galit Alter, Mary Marovich, Merlin L Robb, Michael A Eller, Jeff Martin, Steven Deeks, Nelson L Michael, Hendrik Streeck
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28468011/overcoming-cd8-t-cell-exhaustion-in-viral-hepatitis-lessons-from-the-mouse-model-and-clinical-perspectives
#15
Dominik Wieland, Maike Hofmann, Robert Thimme
About 500 million people all over the world are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and are thus at high risk of developing liver fibrosis, cirrhosis or hepatocellular carcinoma. While in adults about 90% of acutely HBV-infected patients clear the virus, only 30% of acute HCV infections clear spontaneously. Several mechanisms contribute to the failure in viral clearance. The main factors responsible for the chronification of HBV and HCV infection are, on the one hand, viral escape mutations leading to lack of recognition by antiviral immune cells and, on the other hand, loss of antiviral effector functions of virus-specific CD8+ T cells, called T-cell exhaustion...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28466857/tcf1-hepatitis-c-virus-specific-cd8-t-cells-are-maintained-after-cessation-of-chronic-antigen-stimulation
#16
Dominik Wieland, Janine Kemming, Anita Schuch, Florian Emmerich, Percy Knolle, Christoph Neumann-Haefelin, Werner Held, Dietmar Zehn, Maike Hofmann, Robert Thimme
Differentiation and fate of virus-specific CD8(+) T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1(+)CD127(+)PD1(+) hepatitis C virus (HCV)-specific CD8(+) T-cell subset exists in chronically infected patients with phenotypic features of T-cell exhaustion and memory, both before and after treatment with direct acting antiviral (DAA) agents. This subset is maintained during, and for a long duration after, HCV elimination. After antigen re-challenge the less differentiated TCF1(+)CD127(+)PD1(+) population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1(hi) HCV-specific CD8(+) T cells...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28465490/type-i%C3%AE-phosphatidylinositol-phosphate-kinase-regulates-pd-l1-expression-by-activating-nf-%C3%AE%C2%BAb
#17
Junli Xue, Chunhua Chen, Manlong Qi, Yan Huang, Lin Wang, Yong Gao, Haidong Dong, Kun Ling
The programmed death-ligand 1 (PD-L1), by binding to PD-1 on the surface of immune cells, activates a major immune checkpoint pathway. Elevated expression of PD-L1 in tumor cells mediates tumor-induced T-cell exhaustion and immune suppression; therefore protect the survival of tumor cells. Although blockade of the PD-1/PD-L1 axis exhibits great potential in cancer treatment, mechanisms driving the up-regulation of PD-L1 in tumor cells remain not fully understood. Here we found that type Iγ phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIγ) is required for PD-L1 expression in triple negative breast cancer cells...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465192/lung-inflammation-and-genotoxicity-in-mice-lungs-after-pulmonary-exposure-to-candle-light-combustion-particles
#18
Astrid Skovmand, Ana Cecilia Damiao Gouveia, Ismo Kalevi Koponen, Peter Møller, Steffen Loft, Martin Roursgaard
Candle burning produces a large amount of particles that contribute substantially to the exposure to indoor particulate matter. The exposures to various types of combustion particles, such as diesel exhaust particles, have been associated with increased risk of lung cancer by mechanisms that involve oxidative stress, inflammation and genotoxicity. The aim of this study was to compare pulmonary effects of candle light combustion particles (CP) with two benchmark diesel exhaust particles (A-DEP and SRM2975). Intratracheal (i...
April 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28453589/-effects-of-prebiotics-and-probiotics-on-gastrointestinal-tract-lymphoid-tissue-in-hiv-infected-patients
#19
Manuel G Feria, Natalia A Taborda, Juan C Hernandez, María T Rugeles
HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion...
February 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28450868/hepatitis-b-virus-immunopathology-model-systems-and-current-therapies
#20
REVIEW
Praneet Sandhu, Mohammad Haque, Tessa Humphries-Bickley, Swetha Ravi, Jianxun Song
Most people develop acute hepatitis B virus (HBV)-related hepatitis that is controlled by both humoral and cellular immune responses following acute infection. However, a number of individuals in HBV-endemic areas fail to resolve the infection and consequently become chronic carriers. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities...
2017: Frontiers in Immunology
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