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https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#1
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521284/cytokine-mediated-activation-of-human-ex-vivo-expanded-v%C3%AE-9v%C3%AE-2-t-cells
#2
Eisuke Domae, Yuya Hirai, Takashi Ikeo, Seiji Goda, Yoji Shimizu
Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#3
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28393074/adenovirus-mediated-ccr7-and-btla-overexpression-enhances-immune-tolerance-and-migration-in-immature-dendritic-cells
#4
Haiming Xin, Jinhong Zhu, Hongcheng Miao, Zhenyu Gong, Xiaochen Jiang, Xiaoyan Feng, Yalin Tong
Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#5
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28277277/immunoregulation-of-dendritic-cell-subsets-by-inhibitory-receptors-in-urothelial-cancer
#6
Mathieu F Chevalier, Perrine Bohner, Claire Pieraerts, Benoit Lhermitte, Jolanta Gourmaud, Antoine Nobile, Samuel Rotman, Valerie Cesson, Virginie Martin, Anne-Sophie Legris, Florence Dartiguenave, Dalila Gharbi, Laurence De Leval, Daniel E Speiser, Denise Nardelli-Haefliger, Patrice Jichlinski, Laurent Derré
Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs...
June 2017: European Urology
https://www.readbyqxmd.com/read/28253339/correction-the-expression-of-light-was-increased-and-the-expression-of-hvem-and-btla-were-decreased-in-the-t-cells-of-patients-with-rheumatoid-arthritis
#7
Bin Yang, Zhuochun Huang, Weihua Feng, Wei Wei, Junlong Zhang, Yun Liao, Linhui Li, Xinle Liu, Zhiqiang Wu, Bei Cai, Yangjuan Bai, Lanlan Wang
[This corrects the article DOI: 10.1371/journal.pone.0155345.].
2017: PloS One
https://www.readbyqxmd.com/read/28243127/increased-btla-and-hvem-in-gastric-cancer-are-associated-with-progression-and-poor-prognosis
#8
Xiuwen Lan, Sen Li, Hongyu Gao, Abiyasi Nanding, Lina Quan, Chunyan Yang, Shaohua Ding, Yingwei Xue
PURPOSE: Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. PATIENTS AND METHODS: A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28164546/expression-of-b-and-t-lymphocyte-attenuator-in-patients-with-severe-community-acquired-pneumonia-and-the-effect-of-steroid-therapy-in-a-mouse-model
#9
Guoqi Zhou, Daoxin Wang, Daishun Liu, Di Qi, Zhenfeng Liu
BACKGROUND: Severe community-acquired pneumonia (CAP) remains a clinical problem, and the identification of new therapeutic targets may increase the rate of successfully treating patients with severe CAP. B and T lymphocyte attenuator (BTLA) is an immunoglobulin-related membrane protein that may play a vital role in the pathogenesis of infection. However, the effects of BTLA in related to severe CAP involved are unknown. In this study, we investigated potential changes in BTLA expression on lymphocytes in patients with severe CAP and determined how BTLA expression affects a model of LPS-induced acute lung inflammation...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28104239/cd8-t-cells-of-chronic-hcv-infected-patients-express-multiple-negative-immune-checkpoints-following-stimulation-with-hcv-peptides
#10
Muttiah Barathan, Rosmawati Mohamed, Jamuna Vadivelu, Li Yen Chang, Ramachandran Vignesh, Jayalakshmi Krishnan, Panneer Sigamani, Alireza Saeidi, M Ravishankar Ram, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA)...
March 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28056053/soluble-b-and-t-lymphocyte-attenuator-correlates-to-disease-severity-in-sepsis-and-high-levels-are-associated-with-an-increased-risk-of-mortality
#11
Anna Lange, Jonas Sundén-Cullberg, Anders Magnuson, Olof Hultgren
INTRODUCTION AND AIMS: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators. METHODS: 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28046066/htlv-1-bzip-factor-enhances-t-cell-proliferation-by-impeding-the-suppressive-signaling-of-co-inhibitory-receptors
#12
Haruka Kinosada, Jun-Ichirou Yasunaga, Kazuya Shimura, Paola Miyazato, Chiho Onishi, Tomonori Iyoda, Kayo Inaba, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. To enhance cell-to-cell transmission of HTLV-1, the virus increases the number of infected cells in vivo. HTLV-1 bZIP factor (HBZ) is constitutively expressed in HTLV-1 infected cells and ATL cells and promotes T-cell proliferation. However, the detailed mechanism by which it does so remains unknown. Here, we show that HBZ enhances the proliferation of expressing T cells after stimulation via the T-cell receptor...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/27933341/intragenic-variations-in-btla-gene-influence-mrna-expression-of-btla-gene-in-chronic-lymphocytic-leukemia-patients-and-confer-susceptibility-to-chronic-lymphocytic-leukemia
#13
Lidia Karabon, Anna Partyka, Monika Jasek, Ewa Lech-Maranda, Olga Grzybowska-Izydorczyk, Agnieszka Bojarska-Junak, Edyta Pawlak-Adamska, Anna Tomkiewicz, Tadeusz Robak, Jacek Rolinski, Irena Frydecka
The aim of this study was to determine the association between polymorphisms in gene encoding B- and T-lymphocyte attenuator (BTLA) and susceptibility to chronic lymphocytic leukemia (CLL) and their influence on mRNA expression of BTLA gene in T and B cells from CLL patients (pts.). The following BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs76844316, rs16859633, rs9288953, rs2705535, rs1844089, rs2705565, rs2633580 were genotyped with use of TaqMan probes in 321 CLL pts. and in 470 controls...
December 2016: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/27922818/age-related-changes-in-the-gene-expression-profile-of-antigen-specific-mouse-cd8-t-cells-can-be-partially-reversed-by-blockade-of-the-btla-cd160-pathways-during-vaccination
#14
Noor Dawany, Elizabeth M Parzych, Louise C Showe, Hildegund Cj Ertl
We analyzed gene expression profiles of young and aged mouse CD8(+) T cells specific for the nucleoprotein (NP) of influenza A/PR8/34 virus. CD8(+) T cells were stimulated either by the NP antigen expressed in its native form or fused into the herpes virus (HSV)-1 glycoprotein D (gD) protein, which blocks signaling through the immunoinhibitory B and T lymphocyte attenuator (BTLA) and CD160 pathways. We show that NP-specific CD8(+) T cells from aged mice exhibit numerous differences in gene expression compared to NP-specific CD8(+) T cells from young mice, including a significant reduction of expression in genes involved in T cell receptor (TcR) and CD28 signaling...
November 9, 2016: Aging
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identifies-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#15
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
February 2017: Genome Research
https://www.readbyqxmd.com/read/27851922/btla-dendritic-cells-the-regulatory-t-cell-force-awakens
#16
Thomas Simon, Jonathan S Bromberg
The role of dendritic cells (DCs) in the induction of antigen-specific tolerance mediated by extrathymic regulatory T (Treg) cells remains incompletely defined. In this issue of Immunity, Jones et al. (2016) show that BTLA(+)DEC205(+)CD8(+)CD11c(+) DCs efficiently induce peripheral Treg cells via the engagement of HVEM, a receptor for BTLA.
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27793593/immunomodulatory-functions-of-btla-and-hvem-govern-induction-of-extrathymic-regulatory-t-cells-and-tolerance-by-dendritic-cells
#17
Andrew Jones, Jessica Bourque, Lindsey Kuehm, Adeleye Opejin, Ryan M Teague, Cindy Gross, Daniel Hawiger
Dendritic cells (DCs) initiate immunity and also antigen-specific tolerance mediated by extrathymic regulatory T (Treg) cells, yet it remains unclear how DCs regulate induction of such tolerance. Here, we report that efficient induction of Treg cells was instructed by BTLA(+)DEC205(+)CD8(+)CD11c(+) DCs and the immunomodulatory functions of BTLA. In contrast, T cell activation in steady state by total CD11c(+) DCs that include a majority of DCs that do not express BTLA did not induce Treg cells and had no lasting impact on subsequent immune responses...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27784399/-immune-tolerance-mediated-by-tim-3-lag-3-and-btla-and-their-reversion-in-hematological-malignancies-review
#18
Shao-Hua Chen, Xiang-Feng Zha, Yang-Qiu Li
The main mechanism of tumor immune suppression is due to the T cell exhaustion which is mediated by abnormal expression of T-cell immunosuppressive receptors in immune cells. Blocking these molecules may restore partial or all functions of T cells. This article reviews the advance on the role of the newly discovered T cell immuno-suppressive receptors such as TIM-3, LAG-3 and BTLA, including their mediated T cell-immune tolerance and the study of targeted immunotherapy in hematological malignancies, so as to provide the new strategy for immune-targeted therapy for hematological malignancies...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27743606/hepatic-expansion-of-virus-specific-cd8-btla-t-cells-with-regulatory-properties-in-chronic-hepatitis-b-virus-infection
#19
Huaizhou Wang, Beiying Wu, Lei Li, Liang Hu, Jiafei Lin, Cen Jiang, Gang Cai, Qian Shen
Similar to programmed death-1 (PD-1), B and T lymphocyte attenuator (BTLA) is a co-inhibitory molecule of the CD28 family. PD-1 is involved in T cell exhaustion during chronic viral infection. However, the role of BTLA in virus-specific T cells is poorly defined. Here we investigated the expression and function of BTLA in T cells from patients with chronic hepatitis B virus (HBV) infection. The phenotype of peripheral and intrahepatic HBV-specific T cells from 43 patients with chronic HBV infection was assessed by flow cytometry...
January 2017: Cellular Immunology
https://www.readbyqxmd.com/read/27717503/btla-expressing-cd11c-antigen-presenting-cells-in-patients-with-active-tuberculosis-exhibit-low-capacity-to-stimulate-t-cell-proliferation
#20
Wan-Dang Wang, Yu-Chi Gao, Yuan-Bin Lu, Jun-Ai Zhang, Gan-Bin Liu, Bin Kong, Wen-Yu Xiang, You-Chao Dai, Shi-Yan Yu, Yan Jia, Xiao-Xia Fu, Lai-Long Yi, Bin-Ying Zheng, Zheng W Chen, Jixin Zhong, Jun-Fa Xu
Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC)...
January 2017: Cellular Immunology
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