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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...
October 6, 2016: Cellular Immunology
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)...
September 30, 2016: Cellular Immunology
Maria-Luisa Del Rio, Ana Maria Bravo Moral, Carlos Fernandez-Renedo, Leo Buhler, Jose-Antonio Perez-Simon, Olivier Chaloin, Rafael Alvarez Nogal, Maximino Fernandez-Caso, Jose-Ignacio Rodriguez-Barbosa
CD160 is a glycosylphosphatidylinositol-anchored protein of the immunoglobulin superfamily. It exhibits a pattern of expression coincident in humans and mice that is mainly restricted to cytotoxic cells and to all intestinal intraepithelial T lymphocytes. B- and T-lymphocyte attenuator (BTLA) and CD160 interact with cysteine-rich domain 1 of the extracellular region of Herpesvirus entry mediator (HVEM). CD160 engagement by HVEM can deliver inhibitory signals to a small subset of human CD4 T cells and attenuate its proliferation and cytokine secretion, but can also costimulate natural killer cells or intraepithelial lymphocytes...
September 15, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Michael Boice, Darin Salloum, Frederic Mourcin, Viraj Sanghvi, Rada Amin, Elisa Oricchio, Man Jiang, Anja Mottok, Nicolas Denis-Lagache, Giovanni Ciriello, Wayne Tam, Julie Teruya-Feldstein, Elisa de Stanchina, Wing C Chan, Sami N Malek, Daisuke Ennishi, Renier J Brentjens, Randy D Gascoyne, Michel Cogné, Karin Tarte, Hans-Guido Wendel
The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors...
October 6, 2016: Cell
Shi-Fa Zhang, Zong-Sheng Tang, Ling Tong, Xiang-Xiang Tao, Qi-Feng Suo, Xue-Mei Xu
BACKGROUND & AIMS: Probiotics is recognized to promote growth performance and immune function via balancing the intestinal microflora. Live clostridium butyricum and bifidobacterium combined powder (LCBBCP) has been widely to treat intestinal dysbacteriosis in newborns in China. This study was undertaken to investigate the effects of the combined probiotics on the expression of B and T lymphocyte attenuator (BTLA) on CD4(+) T cells and the differentiation of lymphocyte subsets in late preterm infants...
September 10, 2016: Microbial Pathogenesis
Zhenyu Xu, Jing Shen, Maggie Haitian Wang, Tao Yi, Yangyang Yu, Yinxin Zhu, Bo Chen, Jianping Chen, Longfei Li, Minxing Li, Jian Zuo, Hui Jiang, Dexi Zhou, Jiajie Luan, Zhangang Xiao
The B7 gene family has crucial roles in the regulation of adaptive cellular immunity. In cancer, deregulation of co-inhibitory B7 molecules is associated with reduced antitumor immunity and cancer immune evasion. FDA approval of cancer immunotherapy antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)-both ligands of the B7 family-demonstrate the impact of these checkpoint regulators in cancer. Using data from cBioPortal, we performed comprehensive molecular profiling of the 10 currently known B7 family proteins in 105 different cancers...
August 2016: Oncoimmunology
Raj Kurupati, Andrew Kossenkov, Larissa Haut, Senthil Kannan, Zhiquan Xiang, Yan Li, Susan Doyle, Qin Liu, Kenneth Schmader, Louise Showe, Hildegund Ertl
We conducted a 5-year study analyzing antibody and B cell responses to the influenza A virus components of the inactivated influenza vaccine, trivalent (IIV3) or quadrivalent (IIV4) in younger (aged 35-45) and aged (≥65 years of age) Caucasian and African American individuals. Antibody titers to the two influenza A virus strains, distribution of circulating B cell subsets and the blood transcriptome were tested at baseline and after vaccination while expression of immunoregulatory markers on B cells were analyzed at baseline...
August 30, 2016: Oncotarget
Min-Min Chen, Xiao Xiao, Xiang-Ming Lao, Yuan Wei, Rui-Xian Liu, Qiu-Hui Zeng, Jun-Cheng Wang, Fang-Zhu Ouyang, Dong-Ping Chen, Ka-Wo Chan, Dai-Chao Shi, Limin Zheng, Dong-Ming Kuang
: The existence, regulation, and functions of IL21(+) immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21(+) TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4(+) T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5(-)PD-1(lo/-)BTLA(-)CD69(hi) tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells...
October 2016: Cancer Discovery
Emmanouil Papasavvas, Lea F Surrey, Deborah K Glencross, Livio Azzoni, Jocelin Joseph, Tanvier Omar, Michael D Feldman, Anna-Lise Williamson, Maureen Siminya, Avril Swarts, Xiangfan Yin, Qin Liu, Cynthia Firnhaber, Luis J Montaner
Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV(+) women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24)...
May 2016: Oncoimmunology
Ting Zhang, Lei Ye, Lingfei Han, Qizhi He, Jianlong Zhu
Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the immune responses of T lymphocytes. Here, HVEM mRNA was found to be elevated in ovarian cancer tissue samples and primary ovarian cancer cells in comparison with benign tissue samples. We then knocked down HVEM expression in an ovarian cancer cell line, OVCAR3, by lentivirus-based small hairpin RNA (shRNA)...
2016: Oncology Research
Qing Li, Nathan Johnston, Xiufen Zheng, Hongmei Wang, Xusheng Zhang, Dian Gao, Weiping Min
T cell exhaustion is a state of T cell dysfunction that arises during many cancer. miRNAs are one of major gene regulators which result in translational inhibition and/or mRNA degradation. We hypothesized that miRNAs exist that can silence PD1 and act as a modulator in vitro to revert exhaustive status of T cells. We demonstrated that the exhausted T cells with inhibitory receptors (IRs) are significantly increased in the melanoma-bearing mice. Meanwhile, the differentiated miRNA profiles in PD1+ exhaustive T cells were identified using a miRNA array; 11 miRNAs were observed with significant altered levels in the exhausted T cells isolated from melanoma-bearing mice...
July 20, 2016: Oncotarget
Federica Piancone, Marina Saresella, Ivana Marventano, Francesca La Rosa, Martina Zoppis, Simone Agostini, Renato Longhi, Domenico Caputo, Laura Mendozzi, Marco Rovaris, Mario Clerici
B lymphocytes contribute to the pathogenesis of Multiple Sclerosis (MS) by secreting antibodies and producing cytokines. This latter function was analyzed in myelin olygodendrocyte protein (MOG)-stimulated CD19+ B lymphocytes of 71 MS patients with different disease phenotypes and 40 age-and sex-matched healthy controls (HC). Results showed that: 1) CD19+/TNFα+, CD19+/IL-12+ and CD19+/IFNγ+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL-10+/TGFβ+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC...
2016: Scientific Reports
Ying-Nan P Chen, Matthew J LaMarche, Ho Man Chan, Peter Fekkes, Jorge Garcia-Fortanet, Michael G Acker, Brandon Antonakos, Christine Hiu-Tung Chen, Zhouliang Chen, Vesselina G Cooke, Jason R Dobson, Zhan Deng, Feng Fei, Brant Firestone, Michelle Fodor, Cary Fridrich, Hui Gao, Denise Grunenfelder, Huai-Xiang Hao, Jaison Jacob, Samuel Ho, Kathy Hsiao, Zhao B Kang, Rajesh Karki, Mitsunori Kato, Jay Larrow, Laura R La Bonte, Francois Lenoir, Gang Liu, Shumei Liu, Dyuti Majumdar, Matthew J Meyer, Mark Palermo, Lawrence Perez, Minying Pu, Edmund Price, Christopher Quinn, Subarna Shakya, Michael D Shultz, Joanna Slisz, Kavitha Venkatesan, Ping Wang, Markus Warmuth, Sarah Williams, Guizhi Yang, Jing Yuan, Ji-Hu Zhang, Ping Zhu, Timothy Ramsey, Nicholas J Keen, William R Sellers, Travis Stams, Pascal D Fortin
The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway...
July 7, 2016: Nature
Yongan Liu, Wei Nie, Yu Jin, Anshan Zhuo, Yuansheng Zang, Qingyu Xiu
BACKGROUND: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. OBJECTIVE: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. METHODS: Firefly luciferase reporter plasmids pEZX-MT01-wild-type-BTLA and pEZX-MT01-mutant-BTLA were constructed. Lymphocytes were nucleofected with miR-155 inhibitor or negative control (NC)...
June 2016: Iranian Journal of Immunology: IJI
Zong-Sheng Tang, You-Hua Hao, E-Juan Zhang, Chun-Li Xu, Yun Zhou, Xin Zheng, Dong-Liang Yang
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects...
August 2016: Molecular Medicine Reports
Lin Zhang, Jian Wang, Feng Wei, Kaiyuan Wang, Qian Sun, Fan Yang, Hao Jin, Yu Zheng, Hua Zhao, Limei Wang, Wenwen Yu, Xiying Zhang, Yang An, Lili Yang, Xinwei Zhang, Xiubao Ren
Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients. The majority of these molecules, except BTLA, were sharply elevated during the early stage of CIK cell culture...
June 7, 2016: Oncotarget
Anna E Vilgelm, Douglas B Johnson, Ann Richmond
Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests that combining immune-checkpoint inhibitors with other anti-cancer treatments can greatly improve the therapeutic benefit. The first clinical success of the combinatorial approach to cancer immunotherapy was demonstrated using a dual-checkpoint blockade with CTLA-4 and PD-1 inhibitors, which resulted in accelerated FDA approval of this therapeutic regimen...
August 2016: Journal of Leukocyte Biology
Ewa Kozela, Ana Juknat, Fuying Gao, Nathali Kaushansky, Giovanni Coppola, Zvi Vogel
BACKGROUND: Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. METHODS: Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells...
2016: Journal of Neuroinflammation
Scott J Antonia, Johan F Vansteenkiste, Edmund Moon
Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1...
2016: American Society of Clinical Oncology Educational Book
Anna Partyka, Krzysztof Tupikowski, Anna Kolodziej, Romuald Zdrojowy, Agnieszka Halon, Bartosz Malkiewicz, Janusz Dembowski, Irena Frydecka, Lidia Karabon
OBJECTIVE: T cells play an important role in antitumor immunity, and molecules regulating T-cell activity could influence cancer susceptibility. The distinct role of coinhibitory receptors in immunosurveillance has been considered. B- and T-lymphocyte attenuator (BTLA) is one of these receptors, which negatively regulate immune responses. The aim of this study was to investigate the association between BTLA gene polymorphisms and susceptibility to renal cell carcinoma (RCC) in the Polish population...
September 2016: Urologic Oncology
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