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https://www.readbyqxmd.com/read/28710491/ageing-and-latent-cmv-infection-impact-on-maturation-differentiation-and-exhaustion-profiles-of-t-cell-receptor-gammadelta-t-cells
#1
Martine J Kallemeijn, Anne Mieke H Boots, Michèle Y van der Klift, Elisabeth Brouwer, Wayel H Abdulahad, Jan A N Verhaar, Jacques J M van Dongen, Anton W Langerak
Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687760/hypofractionated-stereotactic-radiation-therapy-activates-the-peripheral-immune-response-in-operable-stage-i-non-small-cell-lung-cancer
#2
Ting Zhang, Haifeng Yu, Chao Ni, Tao Zhang, Luying Liu, Qinghua Lv, Zhigang Zhang, Zhen Wang, Dang Wu, Pin Wu, Guodi Chen, Liancong Wang, Qichun Wei, Jian Huang, Xiaojian Wang
It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8(+) T cells, but decreased the frequency of inhibitory Tregs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28671687/recurrent-spi1-pu-1-fusions-in-high-risk-pediatric-t-cell-acute-lymphoblastic-leukemia
#3
Masafumi Seki, Shunsuke Kimura, Tomoya Isobe, Kenichi Yoshida, Hiroo Ueno, Yaeko Nakajima-Takagi, Changshan Wang, Lin Lin, Ayana Kon, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Kyoko Masuda, Hiroshi Kawamoto, Kentaro Ohki, Motohiro Kato, Yuki Arakawa, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Masaharu Akiyama, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Akira Oka, Yasuhide Hayashi, Masatoshi Takagi, Atsushi Manabe, Akira Ohara, Keizo Horibe, Masashi Sanada, Atsushi Iwama, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Junko Takita
The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4(-)CD8(-)) or CD8(+) single-positive (SP) phenotype and had uniformly poor overall survival...
July 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28668505/regulation-of-allergic-airway-inflammation-by-adoptive-transfer-of-cd4-t-cells-preferentially-producing-il-10
#4
Masaya Matsuda, Kana Doi, Tatsuya Tsutsumi, Shinya Fujii, Maki Kishima, Kazuma Nishimura, Ikue Kuroda, Yu Tanahashi, Rino Yuasa, Toshihiko Kinjo, Nobuyuki Kuramoto, Nobuaki Mizutani, Takeshi Nabe
Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4(+) T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days...
June 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28646160/loss-of-g%C3%AE-i-proteins-impairs-thymocyte-development-disrupts-t-cell-trafficking-and-leads-to-an-expanded-population-of-splenic-cd4-pd-1-cxcr5-t-cells
#5
Il-Young Hwang, Kathleen Harrison, Chung Park, John H Kehrl
Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in thymocyte and T cell function, we developed several mouse models. Gαi2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#6
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#7
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28625883/tcr-cd3-cd4-cd8-effector-t-cells-in-psoriasis
#8
D Brandt, M Sergon, S Abraham, K Mäbert, C M Hedrich
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#9
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28588726/pathogenic-mechanism-of-mir-21-in-autoimmune-lymphoid-hyperplasia-syndrome
#10
Yonglong Yan, Xinna Deng, Xiaoran Ning, Fang Li, Jingjing Cao
miR-21 plays an important role in immune responses and inflammatory diseases, but the mechanism of action of miR-21 in autoimmune lymphoid hyperplasia syndrome still remains unclear. The aim of the present study was to assess the mechanism of miR-21 in autoimmune disease, particularly, the autoimmune lymphoid hyperplasia syndrome. The pathology and immunity-related phenotypes of miR-21 transgenic mice, and the lymphocyte subsets were analyzed. The related T cell subsets and germinal center B (GCB) cells generated at the germinal center were detected with flow cytometry...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28579851/transformation-of-follicular-lymphoma-to-a-high-grade-b-cell-lymphoma-with-myc-and-bcl2-translocations-and-overlapping-features-of-burkitt-lymphoma-and-acute-lymphoblastic-leukemia-a-case-report-and-literature-review
#11
Alina M Bischin, Russell Dorer, David M Aboulafia
Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL) with MYC and B-cell lymphoma protein 2 (BCL2) and/or BCL6 gene rearrangements, also known as "double-hit" or "triple-hit" lymphomas. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit...
2017: Clinical Medicine Insights. Blood Disorders
https://www.readbyqxmd.com/read/28577940/trends-practice-patterns-and-underuse-of-surgery-in-the-treatment-of-early-stage-small-cell-lung-cancer
#12
E Wakeam, T K Varghese, N B Leighl, M Giuliani, S R G Finlayson, G E Darling
BACKGROUND: Practice guidelines from the National Comprehensive Cancer Network and the American Society of Clinical Oncology recommend pathologic mediastinal staging and surgical resection for patients with clinically node-negative T1/T2 small cell lung cancer (SCLC), but the extent to which surgery is used is unknown. We sought to assess trends and practice patterns in the use of surgery for SCLC. METHODS: T1 or T2N0M0 SCLC cases were identified in the National Cancer Database (NCDB), 2004-2013...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28571672/targeting-cd147-for-t-to-nk-lineage-reprogramming-and-tumor-therapy
#13
Jie-Jie Geng, Juan Tang, Xiang-Min Yang, Ruo Chen, Yang Zhang, Kui Zhang, Jin-Lin Miao, Zhi-Nan Chen, Ping Zhu
CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28570392/primary-cutaneous-small-cell-variant-of-anaplastic-large-cell-lymphoma-a-case-series-and-review-of-the-literature
#14
Cynthia M Magro, Shabnam Momtahen, Maija Kiuru
Primary cutaneous anaplastic large cell lymphoma (ALCL), similar to systemic ALCL, has as its histomorphologic hallmarks cohesive sheets of large lymphoid cells expressing CD30. Several morphologic variants of systemic ALCL have been reported, including the common (classic) type, lymphohistiocytic, and small cell variants. The small cell variant of ALCL is characterized by a predominant cytomorphology which is unexpected for ALCL, being in the context of a small- to medium-sized hyperchromatic atypical lymphocyte...
May 22, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28553182/ultrastructure-of-hyperfunctioning-parathyroid-glands-does-it-explain-various-patterns-of-99m-tc-sestamibi-uptake
#15
Abdelhamid H Elgazzar, Jehoran T Anim, Shorouk F Dannoon, Medhat M Farghaly
The aim of this study was to correlate the uptake of (99m)Tc-methoxy-isobutyl-isonitrile (MIBI) with ultra-structural features of parathyroid adenomas. Twenty patients with proven primary hyperparathyroidism were evaluated prospectively. Preoperative double-phase (99m)Tc-MIBI scintigraphy was performed in all patients and the degree of tracer uptake by the parathyroid lesions was assessed visually and semi-quantitatively. The excised glands were examined histologically and ultrastructurally, and their features were correlated with the degree of the radiotracer uptake...
April 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28543170/specific-activation-of-cd4-cd8-double-negative-t-cells-by-t-cruzi-derived-glycolipids-induces-a-pro-inflammatory-profile-associated-with-cardiomyopathy-in-chagas-patients
#16
Lívia Silva Araújo Passos, Luísa Mourão Dias Magalhães, Rodrigo Pedro Soares, Alexandre F Marques, Maria do Carmo Pereira Nunes, Kenneth J Gollob, Walderez Ornelas Dutra
Cardiomyopathy is the most severe outcome of Chagas disease, causing over 12,000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. We have shown that CD4-CD8- (double negative - DN) T cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (CARD) and indeterminate (IND) forms of Chagas disease, respectively. Here, we sought to identify Trypanosoma cruzi derived components that lead to activation of DN T cells in Chagas patients...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28515359/t-cell-progenitor-therapy-facilitated-thymopoiesis-depends-upon-thymic-input-and-continued-thymic-microenvironment-interaction
#17
Michelle J Smith, Dawn K Reichenbach, Sarah L Parker, Megan J Riddle, Jason Mitchell, Kevin C Osum, Mahmood Mohtashami, Heather E Stefanski, Brian T Fife, Avinash Bhandoola, Kristin A Hogquist, Georg A Holländer, Juan Carlos Zúñiga-Pflücker, Jakub Tolar, Bruce R Blazar
Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28506538/epitope-specific-immunotherapy-targeting-cd4-positive-t-cells-in-coeliac-disease-two-randomised-double-blind-placebo-controlled-phase-1-studies
#18
Gautam Goel, Tim King, A James Daveson, Jane M Andrews, Janakan Krishnarajah, Richard Krause, Gregor J E Brown, Ronald Fogel, Charles F Barish, Roger Epstein, Timothy P Kinney, Philip B Miner, Jason A Tye-Din, Adam Girardin, Juha Taavela, Alina Popp, John Sidney, Markku Mäki, Kaela E Goldstein, Patrick H Griffin, Suyue Wang, John L Dzuris, Leslie J Williams, Alessandro Sette, Ramnik J Xavier, Ludvig M Sollid, Bana Jabri, Robert P Anderson
BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet...
May 11, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28494925/comparison-of-humoral-and-t-cell-mediated-immune-responses-to-a-single-dose-of-bovela-%C3%A2-live-double-deleted-bvdv-vaccine-or-to-a-field-bvdv-strain
#19
Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A Roth
The objective of this study was to determine and compare the humoral and cellular immune responses of calves exposed to a single dose of Bovela(®) bovine viral diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV) of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old Holstein steer calves that tested negative for persistent BVDV by ear notch immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves were screened by multi-parameter flow cytometry (MP-FCM) 1 week before vaccination to ensure that they were negative for T cell responses to the BVDV types 1 and 2 viruses in the Bovela(®) vaccine...
May 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28490594/dok-1-and-dok-2-are-required-to-maintain-herpes-simplex-virus-1-specific-cd8-t-cells-in-a-murine-model-of-ocular-infection
#20
Soumia Lahmidi, Mitra Yousefi, Slimane Dridi, Pascale Duplay, Angela Pearson
Dok-1 and Dok-2 negatively regulate responses downstream of several immune receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins are essential in the formation of memory CD8(+) T cells to an exogenous epitope expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the control of viral infection is unknown. Herein, we investigated the role of Dok proteins in modulating the immune response against herpes simplex virus 1 (HSV-1) in a mouse model of ocular infection...
May 10, 2017: Journal of Virology
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