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https://www.readbyqxmd.com/read/27933066/functionally-diverse-nk-like-t-cells-are-effectors-and-predictors-of-successful-aging
#1
REVIEW
Joshua J Michel, Patricia Griffin, Abbe N Vallejo
The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27930920/indoleamine-2-3-dioxygenase-regulates-t-cell-activity-through-vav1-rac-pathway
#2
Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#3
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923881/the-ligands-of-translocator-protein-inhibit-human-th1-responses-and-the-rejection-of-murine-skin-allografts
#4
Yannan Zhang, Sifei Yu, Xiaomin Li, Binyan Yang, Changyou Wu
The translocator protein (TSPO) ligands impacted inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the current study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose- dependent manner by purified human CD4(+) T cells from PBMCs after stimulation. TSPO ligands inhibited the production of IFN-γ by memory CD4(+) T cells and the differentiation of naïve CD4(+) T cells into Th1 cells via  suppressing the activity of the corresponding transcription factors as indicated by reduced expression of T-bet and downregulation of STAT1, STAT4 and STAT5 phosphorylation...
December 6, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27920212/inhibition-of-antigen-specific-and-non-specific-stimulation-of-bovine-t-and-b-cells-by-lymphostatin-from-attaching-and-effacing-escherichia-coli
#5
Robin L Cassady-Cain, Elizabeth A Blackburn, Charlotte R Bell, Elizaveta Elshina, Jayne C Hope, Mark P Stevens
Enterohaemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally-encoded 365 kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonisation of cattle by EHEC serogroup O5, O111 and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill-defined...
December 5, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#6
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27911793/heterogeneous-yet-stable-v%C3%AE-2-t-cell-profiles-define-distinct-cytotoxic-effector-potentials-in-healthy-human-individuals
#7
Paul L Ryan, Nital Sumaria, Christopher J Holland, Claire M Bradford, Natalia Izotova, Capucine L Grandjean, Ali S Jawad, Lesley A Bergmeier, Daniel J Pennington
Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2((+))], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2((+)) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2((+)) T-cell biology...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911407/preparation-of-cd4-t-cells-for-analysis-of-gd3-and-gd2-ganglioside-membrane-expression-by-microscopy
#8
Tania M Villanueva-Cabello, Iván Martinez-Duncker
The methods described herein for activation of naïve CD4(+) T cells in suspension and their adherence in coverslips for confocal microscopy analysis allow the spatial localization and visualization of gangliosides involved in CD4(+) T cell activation, that complement expression profiling experiments such as flow cytometry, western blotting or real-time PCR. The quantification of ganglioside expression through flow cytometry and their cellular localization through microscopy can be obtained by the use of anti-ganglioside antibodies with high affinity and specificity...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#9
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#10
Patricia U Simioni, Luis Gr Fernandes, Wirla Msc Tamashiro
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11...
November 30, 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27903736/t-and-b-cell-markers-in-dried-blood-spots-of-neonates-with-congenital-cytomegalovirus-infection-b-cell-numbers-at-birth-are-associated-with-long-term-outcomes
#11
Roberta Rovito, Marjolein J Korndewal, Menno C van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C M Kroes, Anton W Langerak, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#12
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#13
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#14
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27895170/prevention-of-v%C3%AE-9v%C3%AE-2-t-cell-activation-by-a-v%C3%AE-9v%C3%AE-2-tcr-nanobody
#15
Renée C G de Bruin, Anita G M Stam, Anna Vangone, Paul M P van Bergen En Henegouwen, Henk M W Verheul, Zsolt Sebestyén, Jürgen Kuball, Alexandre M J J Bonvin, Tanja D de Gruijl, Hans J van der Vliet
Vγ9Vδ2 T cell activation plays an important role in antitumor and antimicrobial immune responses. However, there are conditions in which Vγ9Vδ2 T cell activation can be considered inappropriate for the host. Patients treated with aminobisphosphonates for hypercalcemia or metastatic bone disease often present with a debilitating acute phase response as a result of Vγ9Vδ2 T cell activation. To date, no agents are available that can clinically inhibit Vγ9Vδ2 T cell activation. In this study, we describe the identification of a single domain Ab fragment directed to the TCR of Vγ9Vδ2 T cells with neutralizing properties...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27893767/t-cells-of-infants-are-mature-but-hyporeactive-due-to-limited-ca2-influx
#16
Kristin Schmiedeberg, Hardy Krause, Friedrich-Wilhelm Röhl, Roland Hartig, Gerhard Jorch, Monika C Brunner-Weinzierl
CD4 T cells in human infants and adults differ in the initiation and strength of their responses. The molecular basis for these differences is not yet understood. To address this the principle key molecular events of TCR- and CD28-induced signaling in naive CD4 T cells, such as Ca2+ influx, NFAT expression, phosphorylation and translocation into the nucleus, ERK activation and IL-2 response, were analyzed over at least the first 3 years of life. We report dramatically reduced IL-2 and TNFα responses in naive CD31+ T cells during infancy...
2016: PloS One
https://www.readbyqxmd.com/read/27891502/diacylglycerol-kinases-in-t-cell-tolerance-and-effector-function
#17
REVIEW
Shelley S Chen, Zhiming Hu, Xiao-Ping Zhong
Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR) signal by recruiting multiple effector molecules, such as RasGRP1, PKCθ, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms, α and ζ, in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27887973/decommissioning-strategy-for-liquid-low-level-radioactive-waste-surface-storage-water-reservoir
#18
S S Utkin, I I Linge
The Techa Cascade of water reservoirs (TCR) is one of the most environmentally challenging facilities resulted from FSUE "PA "Mayak" operations. Its reservoirs hold over 360 mln m(3) of liquid radioactive waste with a total activity of some 5 × 10(15) Bq. A set of actions implemented under a special State program involving the development of a strategic plan aimed at complete elimination of TCR challenges (Strategic Master-Plan for the Techa Cascade of water reservoirs) resulted in considerable reduction of potential hazards associated with this facility...
November 22, 2016: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/27886408/role-of-rock2-in-cd4-cells-in-allergic-airways-responses-in-mice
#19
David I Kasahara, Joel A Mathews, Fernanda M C Ninin, Allison P Wurmbrand, James K Liao, Stephanie A Shore
BACKGROUND: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. OBJECTIVE: To determine the role of ROCK2 acting within CD4(+) cells in allergic airways responses. METHODS: ROCK2 haploinsufficient (ROCK2(+/-) ) and wildtype mice were sensitized with ovalbumin (OVA). ROCK2(+/-) mice then received either CD4(+) cells from ROCK2 sufficient OVA TCR transgenic (OT-II) mice or saline i...
November 25, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27883938/pretreatment-of-activated-human-cd8-t-cells-with-il-12-leads-to-enhanced-tcr-induced-signaling-and-cytokine-production
#20
Aldo Vacaflores, Samantha N Freedman, Nicole M Chapman, Jon C D Houtman
During the immune response to pathogens and autoantigens, CD8T cells are exposed to numerous inflammatory agents including the cytokine IL-12. Previous studies have focused on how IL-12 regulates T cell functions when present during or after the activation of the T cell receptor (TCR). However, recent studies suggest that prior exposure to IL-12 also alters the TCR responsiveness of murine T cells. Whether similar phenomena occur in human activated CD8T cells and the mechanisms mediating these effects remain unexplored...
November 21, 2016: Molecular Immunology
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