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Naïve T cells

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https://www.readbyqxmd.com/read/28345628/tissue-resident-memory-t-cells-in-the-human-conjunctiva-and-immune-signatures-in-human-dry-eye-disease
#1
Tanima Bose, Ryan Lee, Aihua Hou, Louis Tong, K George Chandy
Non-recirculating resident memory (TRM) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract. Using impression cytology followed by flow cytometry we identified two TRM subsets and four recirculating T-subsets in the healthy human ocular surface. In dry eye disease, principal component analysis (PCA) revealed two clusters of patients with distinct T-cell signatures. Increased conjunctival central memory and naïve T cells characterized Cluster-1 patients, and increased CD8(+) TRMs and CD4(+) recirculating memory T cells characterized Cluster-2 patients...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345074/single-cell-rna-seq-and-computational-analysis-using-temporal-mixture-modelling-resolves-th1-tfh-fate-bifurcation-in-malaria
#2
Tapio Lönnberg, Valentine Svensson, Kylie R James, Daniel Fernandez-Ruiz, Ismail Sebina, Ruddy Montandon, Megan S F Soon, Lily G Fogg, Arya Sheela Nair, Urijah Liligeto, Michael J T Stubbington, Lam-Ha Ly, Frederik Otzen Bagger, Max Zwiessele, Neil D Lawrence, Fernando Souza-Fonseca-Guimaraes, Patrick T Bunn, Christian R Engwerda, William R Heath, Oliver Billker, Oliver Stegle, Ashraful Haque, Sarah A Teichmann
Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#3
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#4
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344867/cd4-and-cd8-t-cells-are-both-needed-to-induce-paraneoplastic-neurological-disease-in-a-mouse-model
#5
Christina Gebauer, Béatrice Pignolet, Lidia Yshii, Emilie Mauré, Jan Bauer, Roland Liblau
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#6
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28341672/activation-of-myeloid-tlr4-mediates-t-lymphocyte-polarization-after-traumatic-brain-injury
#7
Molly Braun, Kumar Vaibhav, Nancy Saad, Sumbul Fatima, Darrell W Brann, John R Vender, Lei P Wang, Md Nasrul Hoda, Babak Baban, Krishnan M Dhandapani
Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI...
March 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28337676/logistic-proliferation-of-cells-in-scratch-assays-is-delayed
#8
Wang Jin, Esha T Shah, Catherine J Penington, Scott W McCue, Philip K Maini, Matthew J Simpson
Scratch assays are used to study how a population of cells re-colonises a vacant region on a two-dimensional substrate after a cell monolayer is scratched. These experiments are used in many applications including drug design for the treatment of cancer and chronic wounds. To provide insights into the mechanisms that drive scratch assays, solutions of continuum reaction-diffusion models have been calibrated to data from scratch assays. These models typically include a logistic source term to describe carrying capacity-limited proliferation; however, the choice of using a logistic source term is often made without examining whether it is valid...
March 23, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28332288/tetrandrine-an-agonist-of-aryl-hydrocarbon-receptor-reciprocally-modulates-the-activities-of-stat3-and-stat5-to-suppress-th17-cell-differentiation
#9
Xusheng Yuan, Yannong Dou, Xin Wu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid constituent of the root of Stephania tetrandra S. Moore, was previously shown to suppress the differentiation of T helper 17 (Th17) cells and consequently ameliorate the collagen-induced arthritis (CIA) in mice by activating the aryl hydrocarbon receptor (AhR), but its underlying mechanism is incompletely understood. Here, we investigated how tetrandrine suppressed Th17 cell differentiation through the AhR pathway. The naïve CD4(+) T cells were stimulated with anti-CD3/CD28 for 72 hrs in the presence or absence of tetrandrine under the Th17-polarizing condition...
March 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28332270/changes-in-elevated-cholesterol-in-the-era-of-tenofovir-in-south-africa-risk-factors-clinical-management-and-outcomes
#10
L Jamieson, D Evans, A T Brennan, F Moyo, D Spencer, K Mahomed, M Maskew, L Long, S Rosen, M P Fox
OBJECTIVES: Antiretroviral therapy (ART) has been associated with unfavourable lipid profile changes and increased risk of cardiovascular disease (CVD). With a growing population on ART in South Africa, there has been concern about the increase in noncommunicable diseases such as CVD. We determined risk factors associated with increased total cholesterol (TC) in a large cohort on ART and describe the clinical management thereof. METHODS: We conducted an observational cohort study of ART-naïve adults initiating standard first-line ART in a large urban clinic in Johannesburg, South Africa...
March 23, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28332200/immunoregulation-of-inflammatory-and-inhibitory-cytokines-by-vitamin-d3-in-patients-with-inflammatory-bowel-diseases-ibd
#11
REVIEW
Hussaini Mohammed Alhassan, Abbas Mirshafiey, Homayoun Vahedi, Gholamreza Hemmasi, Ateke Moussavi Nasl Khameneh, Karim Parastouei, Ali Akbar Saboor-Yaraghi
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of Vitamin D3 in IBD patients exerts both direct and indirect regulatory roles on the naïve T-cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of Vitamin D3 on naïve T-cells result in the proliferation of more regulatory T-cells and inhibitory cytokines such as IL-4, IL-10, and IL-5...
March 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28331616/ex-vivo-akt-inhibition-promotes-the-generation-of-potent-cd19car-t-cells-for-adoptive-immunotherapy
#12
Ryan Urak, Miriam Walter, Laura Lim, ChingLam W Wong, Lihua E Budde, Sandra Thomas, Stephen J Forman, Xiuli Wang
BACKGROUND: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331526/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#13
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28330898/antigen-presenting-human-%C3%AE-%C3%AE-t-cells-promote-intestinal-cd4-t-cell-expression-of-il-22-and-mucosal-release-of-calprotectin
#14
Christopher J Tyler, Neil E McCarthy, James O Lindsay, Andrew J Stagg, Bernhard Moser, Matthias Eberl
The cytokine IL-22 plays a critical role in mucosal barrier defense, but the mechanisms that promote IL-22 expression in the human intestine remain poorly understood. As human microbe-responsive Vγ9/Vδ2 T cells are abundant in the gut and recognize microbiota-associated metabolites, we assessed their potential to induce IL-22 expression by intestinal CD4(+) T cells. Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4(+) T cells obtained from human blood or the colon...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28328926/frequency-and-role-of-nkp46-and-nkg2a-in-hepatitis-b-virus-infection
#15
Teppei Yoshioka, Tomohide Tatsumi, Takuya Miyagi, Kaori Mukai, Kumiko Nishio, Akira Nishio, Yoshinobu Yokoyama, Takahiro Suda, Tadashi Kegasawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara
BACKGROUND AND AIM: Natural Killer (NK) cells are involved in the control of viral infection. However, the role of NK cells in chronic hepatitis B (CHB) remains unclear. This study investigated the frequencies and roles of NK cells in CHB, with a focus on activating receptor NKp46 and inhibitory receptor NKG2A. PATIENTS/METHOD: Peripheral blood lymphocytes were obtained from 71 CHB patients and 37 healthy subjects (HS). The expressions of NKp46 and NKG2A were analyzed using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28322752/neuroprotector-effect-of-stem-cells-from-human-exfoliated-deciduous-teeth-transplanted-after-traumatic-spinal-cord-injury-involves-inhibition-of-early-neuronal-apoptosis
#16
Fabrício do Couto Nicola, Marília Rossato Marques, Felipe Odorcyk, Danusa Mar Arcego, Letícia Petenuzzo, Dirceu Aristimunha, Adriana Vizuete, Eduardo Farias Sanches, Daniela Pavulack Pereira, Natasha Maurmann, Carla Dalmaz, Patricia Pranke, Carlos A Netto
Stem cells from human exfoliated deciduous teeth (SHED) transplants have been investigated as a possible treatment strategy for spinal cord injuries (SCI) due to their potential for promoting functional recovery. The aim of present study was to investigate the effects of SHED on neuronal death after an experimental model of SCI. METHODS: Wistar rats were spinalized using NYU impactor®. Animals were randomly distributed into 4 groups: Control (Naive) or Surgical control, Sham (laminectomy with no SCI); SCI (laminectomy followed by SCI, treated with vehicle); SHED (SCI treated with intraspinal transplantation of 3×10(5) SHED, 1 h after SCI)...
March 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28322571/age-associated-dna-methylation-changes-in-naive-cd4-t-cells-suggest-an-evolving-autoimmune-epigenotype-in-aging-t-cells
#17
Mikhail G Dozmorov, Patrick Coit, Kathleen Maksimowicz-McKinnon, Amr H Sawalha
AIM: We sought to define age-associated DNA methylation changes in naive CD4(+) T cells. MATERIALS & METHODS: Naive CD4(+) T cells were collected from 74 healthy individuals (age 19-66 years), and age-related DNA methylation changes were characterized. RESULTS: We identified 11,431 age-associated CpG sites, 57% of which were hypermethylated with age. Hypermethylated sites were enriched in CpG islands and repressive transcription factor binding sites, while hypomethylated sites showed T cell specific enrichment in active enhancers marked by H3K27ac and H3K4me1...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28320969/ena-vasp-proteins-regulate-activated-t-cell-trafficking-by-promoting-diapedesis-during-transendothelial-migration
#18
Miriam L Estin, Scott B Thompson, Brianna Traxinger, Marlie H Fisher, Rachel S Friedman, Jordan Jacobelli
Vasodilator-stimulated phosphoprotein (VASP) and Ena-VASP-like (EVL) are cytoskeletal effector proteins implicated in regulating cell morphology, adhesion, and migration in various cell types. However, the role of these proteins in T-cell motility, adhesion, and in vivo trafficking remains poorly understood. This study identifies a specific role for EVL and VASP in T-cell diapedesis and trafficking. We demonstrate that EVL and VASP are selectively required for activated T-cell trafficking but are not required for normal T-cell development or for naïve T-cell trafficking to lymph nodes and spleen...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320933/activin-a-co-opts-irf4-and-ahr-signaling-to-induce-human-regulatory-t-cells-that-restrain-asthmatic-responses
#19
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Aikaterini I Trochoutsou, Tess M Brodie, Nikolaos Poulos, Konstantinos Samitas, Maria Kapasa, Dimitris Konstantopoulos, Giannis Paraskevopoulos, Mina Gaga, Catherine M Hawrylowicz, Federica Sallusto, Georgina Xanthou
Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4(+) T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320417/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#20
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
March 20, 2017: AIDS Research and Therapy
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