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https://www.readbyqxmd.com/read/28229084/restricted-cd4-t-cell-receptor-repertoire-impairs-cognitive-function-via-alteration-of-th2-cytokine-levels
#1
COMMENT
Eun Ji Song, Seong Gak Jeon, Kyoung Ah Kim, Jin-Il Kim, Minho Moon
Despite the effects of CD4+ T cell dysfunction on cognitive and behavioral impairment are well established, the effects of Th2 cytokines on the adult hippocampal neurogenesis and cognitive function in restricted CD4+ T cell receptor (TCR) repertoire model have not been fully elucidate. We found that mice with restricted CD4+ repertoire TCR showed decreased adult hippocampal neurogenesis using OT-II mice. Moreover, we demonstrated that OT-II mice showed increased Th2 cytokine levels in peripheral organs and IL-4 levels in brain...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#2
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28218745/human-%C3%AE-%C3%AE-t-cells-are-quickly-reconstituted-after-stem-cell-transplantation-and-show-adaptive-clonal-expansion-in-response-to-viral-infection
#3
Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#4
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213049/impaired-nk-cell-functionality-and-increased-tnf-%C3%AE-production-as-biomarkers-of-chronic-chikungunya-arthritis-and-rheumatoid-arthritis
#5
Subrat Thanapati, Mohini Ganu, Prashant Giri, Shruti Kulkarni, Meenal Sharma, Prasad Babar, Ashok Ganu, Anuradha S Tripathy
The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3(-)CD56(+)) and NK-like T (CD3(+)CD56(+)) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-α and IFN-γ-secreting NK-like T cells were high in both chronic arthritis patients than in controls...
February 14, 2017: Human Immunology
https://www.readbyqxmd.com/read/28212502/a-new-mechanism-shapes-the-na%C3%A3-ve-cd8-t-cell-repertoire-the-selection-for-full-diversity
#6
Pedro Gonçalves, Marco Ferrarini, Carmen Molina-Paris, Grant Lythe, Florence Vasseur, Annik Lim, Benedita Rocha, Orly Azogui
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clone sizes...
February 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28202687/oxidized-phagosomal-nox2-is-replenished-from-lysosomes
#7
Ilse Dingjan, Peter T A Linders, Luuk van den Bekerom, Maksim V Baranov, Partho Halder, Martin Ter Beest, Geert van den Bogaart
In dendritic cells, the NADPH oxidase 2 (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome which kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b558, traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b558 is initially recruited to the phagosome from the plasma membrane during phagosome formation...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28196891/insights-into-immune-system-development-and-function-from-mouse-t-cell-repertoires
#8
Zachary Sethna, Yuval Elhanati, Chrissy S Dudgeon, Curtis G Callan, Arnold J Levine, Thierry Mora, Aleksandra M Walczak
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28192476/th40-cells-cd4-cd40-tcells-drive-a-more-severe-form-of-experimental-autoimmune-encephalomyelitis-than-conventional-cd4-t-cells
#9
Gisela M Vaitaitis, Martin G Yussman, Dan M Waid, David H Wagner
CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination...
2017: PloS One
https://www.readbyqxmd.com/read/28190732/the-macronuclear-genome-of-stentor-coeruleus-reveals-tiny-introns-in-a-giant-cell
#10
Mark M Slabodnick, J Graham Ruby, Sarah B Reiff, Estienne C Swart, Sager Gosai, Sudhakaran Prabakaran, Ewa Witkowska, Graham E Larue, Susan Fisher, Robert M Freeman, Jeremy Gunawardena, William Chu, Naomi A Stover, Brian D Gregory, Mariusz Nowacki, Joseph Derisi, Scott W Roy, Wallace F Marshall, Pranidhi Sood
The giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor [1, 2] is a heterotrichous ciliate distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan [3], were attracted to the system because of its regenerative abilities-if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality [2, 3]...
February 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28188172/t-cell-repertoires-in-refractory-coeliac-disease
#11
Julia Ritter, Karin Zimmermann, Korinna Jöhrens, Stefanie Mende, Anke Seegebarth, Britta Siegmund, Steffen Hennig, Kremena Todorova, Andreas Rosenwald, Severin Daum, Michael Hummel, Michael Schumann
OBJECTIVE: Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis...
February 10, 2017: Gut
https://www.readbyqxmd.com/read/28187283/applications-of-immunogenomics-to-cancer
#12
REVIEW
X Shirley Liu, Elaine R Mardis
Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28185879/ctla4-ig-effectively-controls-immune-activation-and-inflammatory-disease-in-a-novel-murine-model-of-leaky-scid
#13
Stéphanie Humblet-Baron, Susann Schönefeldt, Josselyn Garcia-Perez, Frédéric Baron, Emanuela Pasciuto, Adrian Liston
BACKGROUND: Severe combined immunodeficiency (SCID) can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as RAG1, RAG2 or DCLRE1C. Defective DNA recombination causes a developmental block in T cells and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give a partial loss of T cells, in a spectrum including leaky SCID (LS) and Omenn syndrome (OS). These patients not only develop life-threatening infections due to immunodeficiency, but also develop inflammatory/autoimmune conditions due to the presence of autoreactive T cells...
February 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28182271/optimizing-treatment-for-patients-with-alk-positive-lung-cancer
#14
Ibiayi Dagogo-Jack, Alice T Shaw, Gregory J Riely
In the nine years since the initial discovery of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC), there has been tremendous progress, culminating in an ever-expanding repertoire of agents that have activity in this disease. This review article provides an overview of currently approved ALK inhibitors, other ALK inhibitors in development, and commonly described mechanisms of resistance to ALK inhibitors. We also discuss emerging controversies in treatment of patients with ALK positive lung cancer, including the choice of first-line ALK inhibitor and the role of tyrosine kinase inhibitors in the treatment of central nervous system metastases...
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28179494/hierarchical-clustering-can-identify-b-cell-clones-with-high-confidence-in-ig-repertoire-sequencing-data
#15
Namita T Gupta, Kristofor D Adams, Adrian W Briggs, Sonia C Timberlake, Francois Vigneault, Steven H Kleinstein
Adaptive immunity is driven by the expansion, somatic hypermutation, and selection of B cell clones. Each clone is the progeny of a single B cell responding to Ag, with diversified Ig receptors. These receptors can now be profiled on a large scale by next-generation sequencing. Such data provide a window into the microevolutionary dynamics that drive successful immune responses and the dysregulation that occurs with aging or disease. Clonal relationships are not directly measured, but they must be computationally inferred from these sequencing data...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28177966/high-number-of-activated-cd8-t-cells-targeting-hiv-antigens-are-present-in-cerebrospinal-fluid-in-acute-hiv-infection
#16
Cari F Kessing, Serena Spudich, Victor Valcour, Pearline Cartwright, Thep Chalermchai, James L K Fletcher, Carmen Nichols, Benjamin J Josey, Bonnie Slike, Shelly J Krebs, Napapon Sailsuta, Sukalaya Lerdlum, Linda Jagodzinski, Somporn Tipsuk, Duanghathai Suttichom, Somprartthana Rattanamanee, Henrik Zetterberg, Joanna Hellmuth, Nittaya Phanuphak, Merlin L Robb, Nelson L Michael, Jintanat Ananworanich, Lydie Trautmann
BACKGROUND: Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection is unknown. METHODS: We analyzed the phenotype, gene expression, TCR repertoire and HIV-specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of acute HIV infection (AHI) (n=26), chronic (n=23), and uninfected (n=8)...
February 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28177902/identification-of-patient-specific-and-tumor-shared-t-cell-receptor-sequences-in-renal-cell-carcinoma-patients
#17
Chiara Massa, Harlan Robins, Cindy Desmarais, Dagmar Riemann, Corinna Fahldieck, Paolo Fornara, Barbara Seliger
A major requirement for cancer immunotherapy is the development of biomarkers for prognosis and for monitoring therapy response. In an attempt to evaluate the immune response of renal cell carcinoma (RCC) patients, tumor lesions and / or blood samples from 12 RCC patients underwent deep T cell receptor (TCR) sequencing. Despite the low number of samples, different TCR distribution patterns could be detected. Most of the RCC patients presented "patient-specific" TCR sequences, and those clonotypes were present at higher frequency in tumor lesions suggesting a specific extravasation from the blood...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28172804/dop084-peripheral-t-cell-repertoire-reconstitution-in-crohn-s-disease-patients-undergoing-autologous-hsct
#18
A M Corraliza, M C Masamunt, E Ricart, A Lόpez-García, L Le Bourhis, M Allez, J Panés, A Salas
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28172667/dop054-high-throughput-sequencing-of-t-cell-receptors-from-pediatric-ulcerative-colitis-patients-reveals-distinct-tissue-specific-repertoires
#19
L Werner, M Nunberg, Y Haberman, A Lahad, D Turner, B Weiss, D Shouval
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28172441/op004-resetting-of-the-mucosal-t-cell-repertoire-after-hematopoietic-stem-cell-transplantation-in-refractory-crohn-s-disease
#20
L Le Bourhis, A Corraliza, C Auzolle, E Ricart, C Hawkey, J O Lindsay, M Clark, G Rogler, J Satsangui, D Haller, J Panes, A Salas, M Allez
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
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