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T cell subsets

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https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#1
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29040054/pediatric-nut-midline-carcinoma-therapeutic-success-employing-a-sarcoma-based-multimodal-approach
#2
Simone Storck, Alyssa L Kennedy, Karen J Marcus, Lisa Teot, Jennifer Vaughn, Astrid K Gnekow, Bruno Märkl, Ivo Leuschner, Steven G DuBois, Christopher A French, Michael C Frühwald
A subset of poorly differentiated squamous cell carcinomas, NUT midline carcinomas (NMC) are characterized by a translocation t(15;19)(q13;p13) [ 1 ]. The prognosis is generally dismal [ 2 ] and therapeutic success has been limited to exceptional cases [ 3 ]. We present two cases of pediatric NMC from two different institutions treated according to a multimodal sarcoma approach involving surgery, chemotherapy, and focal radiotherapy. One patient has remained in complete continuous remission for over 6 years, while the other is in CR in early follow-up off therapy...
October 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29036304/il-1r-and-myd88-signaling-in-cd4-t-cells-promote-th17-immunity-and-atherosclerosis
#3
Daniel Engelbertsen, Sara Rattik, Maria Wigren, Jenifer Vallejo, Goran Marinkovic, Alexandru Schiopu, Harry Björkbacka, Jan Nilsson, Eva Bengtsson
Aims: The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper subsets. In this study we tested the roles of IL-1R1 and MyD88 signaling in CD4+ T cells in atherosclerosis. Methods and results: We transferred apoe-/-myd88+/+or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared to mice given apoe-/-myd88+/+ CD4+ T cells...
September 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29036021/the-role-of-innate-lymphoid-cells-in-airway-inflammation-evolving-paradigms
#4
Inge Kortekaas Krohn, Suzanne M Bal, Korneliusz Golebski
PURPOSE OF REVIEW: Innate lymphoid cells (ILCs) act as early orchestrators of the immune response, tissue repair, and maintenance of barrier homeostasis. This review summarizes recent findings of the role of ILCs in airway disease and highlights ongoing developments in clinical applications and treatment options. RECENT FINDINGS: On the basis of the transcription factors required for their development and cytokine profiles, ILCs have been classified into three subsets that resemble those of T-helper subtypes...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29035445/expression-of-leukocytic-syncytin-1-in-b-cell-acute-lymphoblastic-leukemia-and-acute-myeloid-leukemia-patients
#5
Yi Sun, Hongyan Zhu, Jianxin Song, Yaxian Jiang, Hongmei Ouyang, Ting Dong, Rui Tao, Xin Fan, Guiqian Zhang
BACKGROUND: Syncytin-1 is improperly expressed in several cancers. However, its expression profile across leukocytes in leukemia patients has not yet been analyzed. METHODS: A total of 50 AML cases and 14 B-cell ALL patients were consecutively recruited. Bone marrow samples were subjected to flow cytometry. Statistical analysis was applied to compare syncytin-1 expression between B-cell ALL and AML across granulocytes, leukemia cells, and T-lymphocytes (including CD3+, CD4+, and CD8+ subsets thereof) and to correlate syncytin-1 expression to leukemia cells and lymphocytes with the T-cell subset percentages...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29035391/a-gammaherpesvirus-provides-protection-against-allergic-asthma-by-inducing-the-replacement-of-resident-alveolar-macrophages-with-regulatory-monocytes
#6
Bénédicte Machiels, Mickael Dourcy, Xue Xiao, Justine Javaux, Claire Mesnil, Catherine Sabatel, Daniel Desmecht, François Lallemand, Philippe Martinive, Hamida Hammad, Martin Guilliams, Benjamin Dewals, Alain Vanderplasschen, Bart N Lambrecht, Fabrice Bureau, Laurent Gillet
The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions...
October 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29035366/cytoplasmic-p53-couples-oncogene-driven-glucose-metabolism-to-apoptosis-and-is-a-therapeutic-target-in-glioblastoma
#7
Wilson X Mai, Laura Gosa, Veerle W Daniels, Lisa Ta, Jonathan E Tsang, Brian Higgins, W Blake Gilmore, Nicholas A Bayley, Mitra Dehghan Harati, Jason T Lee, William H Yong, Harley I Kornblum, Steven J Bensinger, Paul S Mischel, P Nagesh Rao, Peter M Clark, Timothy F Cloughesy, Anthony Letai, David A Nathanson
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29033130/tumor-and-microenvironment-evolution-during-immunotherapy-with-nivolumab
#8
Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter J Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy...
October 11, 2017: Cell
https://www.readbyqxmd.com/read/29033080/reconstitution-of-th17-tc17-and-treg-cells-after-paediatric-haematopoietic-stem-cell-transplantation-impact-of-interleukin-7
#9
Katrine Kielsen, Lars P Ryder, David Lennox-Hvenekilde, Monika Gad, Claus H Nielsen, Carsten Heilmann, Marianne Ifversen, Anders Elm Pedersen, Klaus Müller
Successful reconstitution of T lymphocytes after allogeneic haematopoietic stem cell transplantation (HSCT) is needed to establish the graft-versus-leukaemia effect and an effective anti-microbial defense, but the ratio between functionally different T-cell subsets needs to be balanced to avoid graft-versus-host disease (GVHD). IL-7 is essential for T-cell generation in the thymus and peripheral T-cell homeostasis. High IL-7 levels have been associated with impaired T-cell reconstitution, increased risk of acute GVHD and treatment-related mortality, but the underlying cellular mechanisms behind these associations have not been investigated previously...
October 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/29032101/mitochondrial-activity-in-t-cells
#10
REVIEW
Gabriela Desdín-Micó, Gonzalo Soto-Heredero, María Mittelbrunn
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory responses and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells...
October 12, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29032059/is-the-adaptive-immune-response-in-murine-trypanosoma-cruzi-infection-influenced-by-zinc-supplementation
#11
Cássia Mariana Bronzon da Costa, Marina Del Vecchio Filipin, Fabrícia Helena Santello, Luiz Miguel Pereira, Miriam Paula Alonso Toldo, José Clóvis do Prado Júnior, Ana Amélia Carraro Abrahão
Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease...
October 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29032004/tnfr2-a-novel-target-for-cancer-immunotherapy
#12
REVIEW
Éva S Vanamee, Denise L Faustman
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but exhibit variable efficacy and relapse and can induce autoimmunity. Tumor necrosis factor (TNF) receptor 2 (TNFR2) is a signaling molecule found on the surface of a subset of potent regulatory T cells (Tregs) that can activate the proliferation of these cells through nuclear factor kappa B (NF-κB). TNFR2 is also abundantly expressed on the surface of many human tumors. We propose that blocking TNFR2 might target abundant TNFR2(+) tumor-infiltrating Tregs and directly kill TNFR2-expressing tumors...
October 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29031731/evaluation-of-a-melanocortin-4-receptor-mc4r-agonist-setmelanotide-in-mc4r-deficiency
#13
Tinh-Hai Collet, Béatrice Dubern, Jacek Mokrosinski, Hillori Connors, Julia M Keogh, Edson Mendes de Oliveira, Elana Henning, Christine Poitou-Bernert, Jean-Michel Oppert, Patrick Tounian, Florence Marchelli, Rohia Alili, Johanne Le Beyec, Dominique Pépin, Jean-Marc Lacorte, Andrew Gottesdiener, Rebecca Bounds, Shubh Sharma, Cathy Folster, Bart Henderson, Stephen O'Rahilly, Elizabeth Stoner, Keith Gottesdiener, Brandon L Panaro, Roger D Cone, Karine Clément, I Sadaf Farooqi, Lex H T Van der Ploeg
OBJECTIVE: Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency. METHODS: We studied the effects of Setmelanotide on mutant MC4Rs in cells and the weight loss response to Setmelanotide administration in rodent studies and a human clinical trial...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031659/validity-of-skin-cancer-malignancy-reporting-to-the-organ-procurement-transplant-network-a-cohort-study
#14
Giorgia L Garrett, Joyce T Yuan, Thuzar M Shin, Sarah T Arron
BACKGROUND: The Organ Procurement Transplant Network (OPTN) registry collects data on posttransplant malignancies in solid organ transplant recipients. Complete and accurate registry data on skin cancer is critical for research on epidemiology and interventions. OBJECTIVE: The study goal was to determine the validity of Organ Procurement Transplant Network skin cancer data. METHODS: This cohort study compared reporting of posttransplant squamous cell carcinoma (SCC) and malignant melanoma (MM) in OPTN to medical-record review-derived data from the Transplant Skin Cancer Network (TSCN) database...
October 11, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29031501/dna-methylation-and-transcription-patterns-in-intestinal-epithelial-cells-from-pediatric-patients-with-inflammatory-bowel-diseases-differentiate-disease-subtypes-and-associate-with-outcome
#15
K J Howell, J Kraiczy, K M Nayak, M Gasparetto, A Ross, C Lee, T N Mak, B-K Koo, N Kumar, T Lawley, A Sinha, P Rosenstiel, R Heuschkel, O Stegle, M Zilbauer
BACKGROUND & AIMS: We analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IEC) of children newly diagnosed with inflammatory bowel diseases (IBD) to learn more about pathogenesis. METHODS: We obtained mucosal biopsies (n=236) collected from terminal ileum and ascending and sigmoid colons of children (median age=13) newly diagnosed with IBD (43 with Crohn's disease [CD], 23 with ulcerative colitis [UC]), and 30 children without IBD (controls)...
October 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29030900/computational-flow-cytometry-analysis-reveals-a-unique-immune-signature-of-the-human-maternal-fetal-interface
#16
Jessica Vazquez, Melina Chavarria, Yan Li, Gladys E Lopez, Aleksandar K Stanic
PROBLEM: Decidual immune dysregulation is thought to underlie major pregnancy disorders; however, incomplete understanding of the decidual immune interface has hampered the mechanistic investigation. METHOD OF STUDY: Human term decidua was collected, and single-cell phenotypic information was acquired by highly polychromatic flow cytometry. Cellular identity analysis was performed with t-distributed stochastic neighbor embedding, DensVM clustering, and matched to CellOntology database...
October 14, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29029943/bcg-immune-activation-reduces-growth-and-angiogenesis-in-an-in-vitro-model-of-head-and-neck-squamous-cell-carcinoma
#17
Carolina Sánchez-Rodríguez, Keyliz Peraza Cruces, Juan Riestra Ayora, Eduardo Martín-Sanz, Ricardo Sanz-Fernández
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide and is associated with poor survival and significant treatment morbidity. The immune profile in patients with HNSCC is immunosuppressive and presents cytokine-mediated adaptive immune responses, triggered apoptosis of T cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin (BCG) immunotherapy has been used successfully as a treatment for several types of cancer. In the present study, we sought to determine the antitumor effect of soluble mediators from peripheral blood mononuclear immune cells (PBMCs) activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth using FaDu hypopharynx carcinoma squamous cells...
October 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29029512/pd-l1-expression-indicates-favorable-prognosis-for-advanced-lung-adenocarcinoma-patients-treated-with-pemetrexed
#18
Pei Zhang, Zhang Bao, Liming Xu, Jianya Zhou, Guohua Lu, Yinan Yao, Rong Liu, Qiqi Gao, Yihong Shen, Jianying Zhou
Conventional chemotherapy for lung cancer exerts anti-tumor effects through cytotoxicity, and through immunologic regulation by reducing specific T cell subsets and inducing the expression of programmed death ligand 1 (PD-L1) on tumor cells. Even though pemetrexed has shown huge potential in combination with other targeted or immune therapies, there is still little information about the values of specific immune checkpoint markers for advanced lung adenocarcinoma treated with pemetrexed. In the present study, a total of 56 patients with advanced lung adenocarcinoma, who received pemetrexed-based chemotherapy, were included retrospectively...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#19
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029332/identification-of-a-novel-subset-of-myeloid-derived-suppressor-cells-during-chronic-staphylococcal-infection-that-resembles-immature-eosinophils
#20
Oliver Goldmann, Andreas Beineke, Eva Medina
We have previously reported that myeloid-derived suppressor cells (MDSC), which are a heterogeneous population of immunosuppressive immature myeloid cells, expanded during chronic Staphylococcus aureus infection and promoted bacterial persistence by inhibiting effector T cells. Two major MDSC subsets including monocytic MDSCs (M-MDSC) and granulocytic MDSCs (G-MDSC) have been described to date. Here, we identified a new subset of MDSC (Eo-MDSC) in S. aureus-infected mice that phenotypically resembles eosinophils...
September 23, 2017: Journal of Infectious Diseases
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