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https://www.readbyqxmd.com/read/27901484/gene-expression-profiling-of-hematologic-malignant-cell-lines-resistant-to-oncolytic-virus-treatment
#1
Nam Hee Lee, Mikyung Kim, Sung Yong Oh, Seong-Geun Kim, Hyuk-Chan Kwon, Tae-Ho Hwang
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#2
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27869818/tcr%C3%AE-tcr%C3%AE-pairing-controls-recognition-of-cd1d-and-directs-the-development-of-adipose-nkt-cells
#3
Joshua A Vieth, Joy Das, Fanomezana M Ranaivoson, Davide Comoletti, Lisa K Denzin, Derek B Sant'Angelo
The interaction between the T cell antigen receptor (TCR) expressed by natural killer T cells (NKT cells) and the antigen-presenting molecule CD1d is distinct from interactions between the TCR and major histocompatibility complex (MHC). Our molecular modeling suggested that a hydrophobic patch created after TCRα-TCRβ pairing has a role in maintaining the conformation of the NKT cell TCR. Disruption of this patch ablated recognition of CD1d by the NKT cell TCR but not interactions of the TCR with MHC. Partial disruption of the patch, while permissive to the recognition of CD1d, significantly altered NKT cell development, which resulted in the selective accumulation of adipose-tissue-resident NKT cells...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27863541/cellular-endocytic-compartment-localization-of-expressed-canine-cd1-molecules
#4
Mette Schjaerff, Stefan M Keller, Verena K Affolter, Annemarie T Kristensen, Peter F Moore
CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and present a variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that survey distinct cellular compartments allowing for recognition of a large repertoire of lipids. The canine CD1 family consists of seven functional CD1 molecules (canine CD1a2, CD1a6, CD1a8, CD1a9, CD1b, CD1c and CD1e) and one presumed non-functional isoform (canine CD1d) due to a disrupted gene structure...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27863214/type-ii-natural-killer-t-cells-that-recognize-sterol-carrier-protein-2-are-implicated-in-vascular-inflammation-in-the-rat-model-of-systemic-connective-tissue-diseases
#5
Yusuke Nishioka, Madoka Yamaguchi, Ai Kawakami, Maya Munehiro, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu
We previously generated a rat model that developed systemic connective tissue diseases, including synovitis, myositis, and small-vessel vasculitis (SVV), and established a vascular endothelial cell-reactive T-cell clone, VASC-1, from the model. VASC-1 was determined to be a type II natural killer T-cell clone. In this study, we attempted to identify the antigen recognized by VASC-1. The monkey-derived cell line COS-7 was used because VASC-1 does not bind naturally to COS-7, although the amino acid sequences are well conserved between monkey CD1d and rat CD1d...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27837018/role-of-dendritic-cell-maturation-factors-produced-by-human-invariant-nkt-cells-in-immune-tolerance
#6
Hyeong-Woo Lee, Hyun Bae Jie, Paul L Bollyky, David Sarracino, Tong-Soo Kim, Brian S Wilson
In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4(+) iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4(+) iNKT cells...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27821872/enterogenous-bacterial-glycolipids-are-required-for-the-generation-of-natural-killer-t-cells-mediated-liver-injury
#7
Yingfeng Wei, Benhua Zeng, Jianing Chen, Guangying Cui, Chong Lu, Wei Wu, Jiezuan Yang, Hong Wei, Rufeng Xue, Li Bai, Zhi Chen, Lanjuan Li, Kazuya Iwabuchi, Toshimitsu Uede, Luc Van Kaer, Hongyan Diao
Glycolipids are potent activator of natural killer T (NKT) cells. The relationship between NKT cells and intestinal bacterial glycolipids in liver disorders remained unclear. We found that, in sharp contrast to specific pathogen-free (SPF) mice, germ-free (GF) mice are resistant to Concanavalin A (ConA)-induced liver injury. ConA treatment failed to trigger the activation of hepatic NKT cells in GF mice. These defects correlated with the sharply reduced levels of CD1d-presented glycolipid antigens in ConA-treated GF mice compared with SPF counterparts...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27801602/a-potent-adjuvant-effect-of-a-cd1d-binding-nkt-cell-ligand-in-human-immune-system-mice
#8
Xiangming Li, Jing Huang, Izumi Kaneko, Min Zhang, Shiroh Iwanaga, Masao Yuda, Moriya Tsuji
OBJECTIVES: A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice. METHODS: HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells...
November 16, 2016: Expert Review of Vaccines
https://www.readbyqxmd.com/read/27799307/nkt-cell-deficient-mice-harbor-an-altered-microbiota-that-fuels-intestinal-inflammation-during-chemically-induced-colitis
#9
Thirumahal Selvanantham, Qiaochu Lin, Cynthia Xinyi Guo, Anuradha Surendra, Stephanie Fieve, Nichole K Escalante, David S Guttman, Catherine J Streutker, Susan J Robertson, Dana J Philpott, Thierry Mallevaey
NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27799287/cd1d-mediated-activation-of-group-3-innate-lymphoid-cells-drives-il-22-production
#10
Julia Saez de Guinoa, Rebeca Jimeno, Nazanin Farhadi, Peter J Jervis, Liam R Cox, Gurdyal S Besra, Patricia Barral
Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid-dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid-presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR)(-)CCR6(+) cells displayed the highest levels of CD1d...
October 31, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27798168/discrete-tcr-binding-kinetics-control-invariant-nkt-cell-selection-and-central-priming
#11
Mayra Cruz Tleugabulova, Nichole K Escalante, Shenglou Deng, Stephanie Fieve, June Ereño-Orbea, Paul B Savage, Jean-Philippe Julien, Thierry Mallevaey
Invariant NKT (iNKT) cells develop and differentiate in the thymus, segregating into iNKT1/2/17 subsets akin to Th1/2/17 classical CD4(+) T cells; however, iNKT TCRs recognize Ags in a fundamentally different way. How the biophysical parameters of iNKT TCRs influence signal strength in vivo and how such signals affect the development and differentiation of these cells are unknown. In this study, we manipulated TCRs in vivo to generate clonotypic iNKT cells using TCR retrogenic chimeras. We report that the biophysical properties of CD1d-lipid-TCR interactions differentially impacted the development and effector differentiation of iNKT cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795360/local-induction-of-b-cell-il-10-competency-alleviates-inflammation-and-bone-loss-in-ligature-induced-experimental-periodontitis-in-mice
#12
Pei Yu, Yang Hu, Zhiqiang Liu, Toshihisa Kawai, Martin A Taubman, Wei Li, Xiaozhe Han
IL-10-producing B cells (B10 cells) play a critical role in immune system balance by negatively regulating inflammatory responses. This study was to determine the effect of local B10 induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitis in vivo Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and Toll-like receptor 9 (TLR9) agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 induction in vitro Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on Day 0 followed by the injections of CD40L and CpG into the palatal gingiva on Days 3, 6, and 9...
October 17, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27787577/alpha-n-acetyl-neuraminide-alpha-2-8-sialyltransferase-1-can-support-immune-responses-toward-tumors-overexpressing-ganglioside-d3-in-mice
#13
Jonathan M Eby, Levi Barse, Steven W Henning, Martijn J W E Rabelink, Jared Klarquist, Emily R Gilbert, Adam M Hammer, Manuel F Fernandez, Nathan Yung, Safia Khan, Hannah G Miller, Edward R Kessler, Elizabeth Garrett-Mayer, Daniel F Dilling, Rob C Hoeben, I Caroline Le Poole
An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d(+)GD3(+) tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3...
October 27, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27782396/phenyl-glycolipids-with-different-glycosyl-groups-exhibit-marked-differences-in-murine-and-human-inkt-cell-activation
#14
Tai-Na Wu, Kun-Hsien Lin, Ying-Ta Wu, Jing-Rong Huang, Jung-Tung Hung, Jen-Chine Wu, Chien-Yu Chen, Kuo-Ching Chu, Nan-Horng Lin, Alice L Yu, Chi-Huey Wong
Glycosphingolipids (GSLs) bearing the α-galactosyl head group and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) to stimulate both murine and human invariant natural killer T (iNKT) cells and to induce antibody isotope switch to IgG. In this study, we replaced the galactosyl group with glucose (αGlc) and its fluoro-analogs, and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal in stimulating human iNKT cells but weaker in mice...
October 26, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27757307/cd1b-autoreactive-t-cells-recognize-phospholipid-antigens-and-contribute-to-antitumor-immunity-against-a-cd1b-t-cell-lymphoma
#15
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27714067/synthesis-self-assembly-and-immunological-activity-of-%C3%AE-galactose-functionalized-dendron-lipid-amphiphiles
#16
John F Trant, Namrata Jain, Delfina M Mazzuca, James T McIntosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth R Gillies
Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron-lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron-lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties...
October 14, 2016: Nanoscale
https://www.readbyqxmd.com/read/27693617/myeloid-derived-suppressor-cells-expressing-a-self-antigen-ameliorate-experimental-autoimmune-encephalomyelitis
#17
Silvia Casacuberta-Serra, Carme Costa, Herena Eixarch, María José Mansilla, Sergio López-Estévez, Lluís Martorell, Marta Parés, Xavier Montalban, Carmen Espejo, Jordi Barquinero
Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms...
September 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27668799/a-three-stage-intrathymic-development-pathway-for-the-mucosal-associated-invariant-t-cell-lineage
#18
Hui-Fern Koay, Nicholas A Gherardin, Anselm Enders, Liyen Loh, Laura K Mackay, Catarina F Almeida, Brendan E Russ, Claudia A Nold-Petry, Marcel F Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J Corbett, Sidonia B G Eckle, Bronwyn Meehan, Yves d'Udekem, Igor E Konstantinov, Martha Lappas, Ligong Liu, Chris C Goodnow, David P Fairlie, Jamie Rossjohn, Mark M Chong, Katherine Kedzierska, Stuart P Berzins, Gabrielle T Belz, James McCluskey, Adam P Uldrich, Dale I Godfrey, Daniel G Pellicci
Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization...
September 26, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27667759/b10-cells-play-a-role-in-the-immune-modulation-of-pro-and-anti-inflammatory-immune-responses-in-mouse-islet-allograft-rejection
#19
Yao Qin, Mei Zhang, Rui-Mei Jiang, Qian Wu, Xin-Yu Xu, Heng Chen, Tao Yang
Recently, pancreatic islet transplantation has been shown to be a viable option for the treatment of type 1 diabetes mellitus. However, immune destruction becomes the major impediment to the clinical application of islet transplantation. Here, we evaluated changes affecting multiple types of immune cells and cytokines in allogeneic islet transplantation immunity after the administration of B10 cells alone and explored the regulatory mechanisms of B10 cells in T cell-mediated allograft rejection. In vitro assays, B10 cells significantly decreased the proliferative capacity of CD4(+)CD25(-) T cells (13...
September 19, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27662666/tim-4-is-expressed-on-invariant-nkt-cells-but-dispensable-for-their-development-and-function
#20
Xilin Zhang, Jun Gu, Li Zhou, Qing-Sheng Mi
T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes...
September 20, 2016: Oncotarget
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