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Naïve T cells

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https://www.readbyqxmd.com/read/28822719/thalidomide-is-associated-with-increased-t-cell-activation-and-inflammation-in-antiretroviral-naive-hiv-infected-individuals-in-a-randomised-clinical-trial-of-efficacy-and-safety
#1
Tânia R C Vergara, Sadia Samer, Joanna R Santos-Oliveira, Leila B Giron, Muhammad Shoaib Arif, Maria Luciana Silva-Freitas, Lia A Cherman, Mauro S Treitsman, Alberto Chebabo, Maria Cecilia A Sucupira, Alda M Da-Cruz, Ricardo Sobhie Diaz
TRIAL DESIGN: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. METHODS: Participants: Antiretroviral naïve adult males with CD4 count ≥350cells/mm(3). INTERVENTIONS: Patients were randomised to receive thalidomide 200mg QD for 3weeks (Thalidomide group) or not (Control group) and followed for 48weeks. OBJECTIVE: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naïve HIV infected individuals...
August 12, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28821585/a-coronin-1-dependent-decision-switch-in-juvenile-mice-determines-the-population-of-the-peripheral-naive-t-cell-compartment
#2
Mathias Jakob Lang, Mayumi Mori, Julie Ruer-Laventie, Jean Pieters
Following thymic maturation, T cells egress as recent thymic emigrants to peripheral lymphoid organs where they undergo an additional maturation step to mature naive T cells that circulate through secondary lymphoid organs ready to be activated upon pathogenic challenges. Thymic maturation and peripheral T cell survival depend on several signaling cascades, but whether a dedicated mechanism exists that exclusively regulates homeostasis of mature naive T cells without affecting thymocytes and/or recent thymic emigrants remains unknown...
August 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28819257/cytolytic-dna-vaccine-encoding-lytic-perforin-augments-the-maturation-of-and-antigen-presentation-by-dendritic-cells-in-a-time-dependent-manner
#3
Danushka K Wijesundara, Wenbo Yu, Ben J C Quah, Preethi Eldi, John D Hayball, Kerrilyn R Diener, Ilia Voskoboinik, Eric J Gowans, Branka Grubor-Bauk
The use of cost-effective vaccines capable of inducing robust CD8(+) T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8(+) T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8(+) T cell immunity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#4
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28817118/altered-marginal-zone-and-innate-like-b-cells-in-aged-senescence-accelerated-samp8-mice-with-defective-igg1-responses
#5
Isabel Cortegano, Mercedes Rodríguez, Isabel Martín, Maria Carmen Prado, Carolina Ruíz, Rafael Hortigüela, Mario Alía, Marçal Vilar, Helena Mira, Eva Cano, Mercedes Domínguez, Belén de Andrés, María Luisa Gaspar
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19(+)CD45R(+)CD21(++)CD23(lo)) and a decrease of naive B cells (CD19(+)IgD(+)), whereas there is an enhancement of a CD19(+)CD45R(lo) innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R(+)CD21(lo)CD23(lo)CD5(-)CD11b(-)) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28814669/neonatal-and-adult-recent-thymic-emigrants-produce-il-8-and-express-complement-receptors-cr1-and-cr2
#6
Marcin L Pekalski, Arcadio Rubio García, Ricardo C Ferreira, Daniel B Rainbow, Deborah J Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E Stevens, Neil M Walker, Antony J Cutler, Frank Waldron-Lynch, David B Dunger, Claire Shannon-Lowe, Alasdair J Coles, Joanne L Jones, Chris Wallace, John A Todd, Linda S Wicker
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812869/entry-inhibitors-a-perspective-for-prevention-of-hepatitis-c-virus-infection-in-organ-transplantation
#7
Che C Colpitts, Raymond T Chung, Thomas F Baumert
Entry inhibitors are emerging as an attractive class of therapeutics for hepatitis C virus (HCV) infection. Entry inhibitors target either virion-associated factors or cellular factors necessary for infection. By blocking entry into cells, entry inhibitors prevent both the establishment of persistent reservoirs and the emergence of resistant variants during viral replication. Furthermore, entry inhibitors protect naïve cells from virus-induced alterations. Combining entry inhibitors with direct-acting antivirals (DAAs) may therefore improve treatment outcomes, particularly in the context of organ transplantation...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28811978/development-and-characterization-of-naive-single-type-tumor-antigen-specific-cd8-t-lymphocytes-from-murine-pluripotent-stem-cells
#8
Fengyang Lei, Mohammad Haque, Praneet Sandhu, Swetha Ravi, Jianyong Song, Bing Ni, Songguo Zheng, Deyu Fang, Hongyan Jia, Jin-Ming Yang, Jianxun Song
Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28809557/in-silico-and-in-vitro-interactions-between-short-chain-fatty-acids-and-human-histone-deacetylases
#9
Rou Hui Ho, James Chun Yip Chan, Hao Fan, Dorinda Yan Qin Kioh, Bee Wah Lee, Eric Chun Yong Chan
Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses. We investigated the structure-inhibition relationships of SCFAs with class I HDAC3 and class IIa HDAC7 using in silico docking simulation and in vitro human recombinant HDAC inhibition assay...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28807247/interleukins-as-new-prognostic-genetic-biomarkers-in-non-small-cell-lung-cancer
#10
Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Ahmed Alnatsha, Miguel Ángel Molina, Ana I Robles, Eduardo Villar, Juan Ramón Delgado, María José Faus-Dáder, Miguel Ángel Calleja-Hernández
BACKGROUND: Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28805723/hitting-the-holy-grail-of-hematopoietic-cell-transplantation-with-naive-t-cell-depleted-allografts-graft-engineered-hematopoietic-stem-cell-transplant
#11
Riad El Fakih, Shahrukh K Hashmi
Hematopoietic cell transplant is a potentially curative procedure for many benign and malignant conditions. The efficacy of allogeneic transplant relies in part on the cytotoxicity of the conditioning regimen and the graft versus tumor effect mediated by alloreactive donor T cells; the same cells are also implicated in the development of graft versus host disease (GVHD). Selective identification and depletion of the T cells implicated in GVHD, while preserving the T cells responsible for graft versus tumor effect has been the focus of many research groups in the recent years...
August 14, 2017: Biomedicines
https://www.readbyqxmd.com/read/28805019/cd11b-gr1-dim-tolerogenic-dendritic-cell-like-cells-are-expanded-in-interstitial-lung-disease-in-skg-mice
#12
Sho Sendo, Jun Saegusa, Takaichi Okano, Soshi Takahashi, Kengo Akashi, Akio Morinobu
OBJECTIVE: SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD (RA-ILD) in human. The aim of this study is to clarify the mechanism behind the lung pathology by analyzing the lung-infiltrating cells in ILD of SKG mice. METHODS: We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4)...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28803798/radiosynthesis-and-preclinical-pet-evaluation-of-89-zr-nivolumab-bms-936558-in-healthy-non-human-primates
#13
Erin L Cole, Joonyoung Kim, David J Donnelly, R Adam Smith, Daniel Cohen, Virginie Lafont, Paul E Morin, Richard Y-C Huang, Patrick L Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28803568/history-of-child-maltreatment-and-telomere-length-in-immune-cell-subsets-associations-with-stress-and-attachment-related-hormones
#14
Christina Boeck, Sabrina Krause, Alexander Karabatsiakis, Katharina Schury, Harald Gündel, Christiane Waller, Iris-Tatjana Kolassa
Experiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels...
August 14, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28802258/human-blood-tfr-cells-are-indicators-of-ongoing-humoral-activity-not-fully-licensed-with-suppressive-function
#15
Valter R Fonseca, Ana Agua-Doce, Ana Raquel Maceiras, Wim Pierson, Filipa Ribeiro, Vasco C Romão, Ana Rita Pires, Susana Lopes da Silva, João Eurico Fonseca, Ana E Sousa, Michelle A Linterman, Luis Graca
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and are crucial for the generation of high-affinity antibodies. Although the biology of human circulating and tissue Tfh cells has been established, the relationship between blood and tissue Tfr cells defined as CXCR5(+)Foxp3(+) T cells remains elusive. We found that blood Tfr cells are increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination...
August 11, 2017: Science Immunology
https://www.readbyqxmd.com/read/28799643/sebocytes-contribute-to-skin-inflammation-by-promoting-the-differentiation-of-th17-cells
#16
M Mattii, M Lovászi, N Garzorz, A Atenhan, M Quaranta, F Lauffer, A Konstantinow, M Küpper, C C Zouboulis, L Kemeny, K Eyerich, C B Schmidt-Weber, D Törőcsik, S Eyerich
BACKGROUND: The main function of sebocytes is considered to be the lipid production for moisturizing the skin. However, it became recently apparent that sebocytes release chemokines and cytokines and respond to pro-inflammatory stimuli as well as presence of bacteria. OBJECTIVES: To analyze the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and IL-17 were performed on acne sections and healthy skin...
August 11, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28797461/the-importance-of-log-odds-of-positive-lymph-nodes-for-locoregional-recurrence-in-oral-squamous-cell-carcinoma
#17
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Uta Drebber, Joachim Zöller, Matthias Kreppel
OBJECTIVES: Log odds of positive lymph nodes (LODDS) has been demonstrated as a very promising staging model for multiple cancer sites, as it avoids singularity and predicts prognosis significantly better than conventional nodal staging and lymph node ratio. However, published studies on the influence of LODDS for patients with OSCC are very seldom. MATERIAL AND METHODS: Retrospective chart review of 499 patients with treatment-naive oral squamous cell carcinoma...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28797028/characterisation-of-the-cancer-associated-glucocorticoid-system-key-role-of-11%C3%AE-hydroxysteroid-dehydrogenase-type-2
#18
Nicola Cirillo, David J Morgan, Maria Carmela Pedicillo, Antonio Celentano, Lorenzo Lo Muzio, Michael J McCullough, Stephen S Prime
BACKGROUND: Recent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers. METHODS: The presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28796194/a-murine-model-of-persistent-inflammation-immune-suppression-and-catabolism-syndrome
#19
Amanda M Pugh, Nicholas J Auteri, Holly S Goetzman, Charles C Caldwell, Vanessa Nomellini
Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen...
August 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#20
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 9, 2017: Nature
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