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https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#1
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28096507/de-novo-phosphorylation-and-conformational-opening-of-the-tyrosine-kinase-lck-act-in-concert-to-initiate-t-cell-receptor-signaling
#2
Lars Philipsen, Amarendra V Reddycherla, Roland Hartig, Janine Gumz, Matthias Kästle, Andreas Kritikos, Mateusz P Poltorak, Yury Prokazov, Evgeny Turbin, André Weber, Werner Zuschratter, Burkhart Schraven, Luca Simeoni, Andreas J Müller
The enzymatic activity of the Src family tyrosine kinase p56(Lck) (Lck) is tightly controlled by differential phosphorylation of two tyrosine residues, Tyr(394) and Tyr(505) Phosphorylation of Tyr(394) and the conformational opening of Lck are believed to activate the kinase, whereas Tyr(505) phosphorylation is thought to generate a closed, inactive conformation of Lck. We investigated whether the conformation of Lck and its phosphorylation state act in concert to regulate the initiation of T cell receptor (TCR) signaling...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28095433/bj-3105-a-6-alkoxypyridin-3-ol-analog-impairs-t-cell-differentiation-and-prevents-experimental-autoimmune-encephalomyelitis-disease-progression
#3
Maheshwor Timilshina, Youra Kang, Ishmit Dahal, Zhiwei You, Tae-Gyu Nam, Keuk-Jun Kim, Byeong-Seon Jeong, Jae-Hoon Chang
CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement...
2017: PloS One
https://www.readbyqxmd.com/read/28087912/-t-cell-receptor-%C3%AE-chain-cdr3-spectratyping-and-cytomegalovirus-activation-in-allogeneic-hematopoietic-stem-cell-transplant-recipients
#4
Zhihua Wu, Min Jing, Hanying Liang, Rong Yang, Yaping Huang, Xiaoming Chen, Jianhua Hu, Jun Fan
Objective: To explore the association between T-cell receptor beta variable (TCR BV) complementarity determining region 3 (CDR3) spectratyping and CMV activation in the recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Methods: Fluorescence quantitative PCR melting curve analysis was used to sequence 24 TCR BV families in 7 HSCT recipients and 3 healthy controls. CMV-pp65 antigenemia was measured by immunohistochemical staining. Plasma IgM specific for CMV was identified using ELISA. Relationship between TCR BV families and CMV activation was statistically analyzed...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#5
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#6
Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria-Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe Matarese, Sergio Abrignani, Paola de Candia
Upon TCR stimulation, CD4+ T lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro TCR stimulation of Th1, Th17 and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared to those released by the other subsets...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076364/ifn%C3%AE-regulates-activated-v%C3%AE-2-t-cells-through-a-feedback-mechanism-mediated-by-mesenchymal-stem-cells
#7
Karoline Fechter, Akaitz Dorronsoro, Emma Jakobsson, Izaskun Ferrin, Valérie Lang, Pilar Sepulveda, Daniel J Pennington, César Trigueros
γδ T cells play a role in a wide range of diseases such as autoimmunity and cancer. The majority of circulating human γδ T lymphocytes express a Vγ9Vδ2+ (Vδ2+) T cell receptor (TCR) and following activation release pro-inflammatory cytokines. In this study, we show that IFNγ, produced by Vδ2+ cells, activates mesenchymal stem cell (MSC)-mediated immunosupression, which in turn exerts a negative feedback mechanism on γδ T cell function ranging from cytokine production to proliferation. Importantly, this modulatory effect is limited to a short period of time (<24 hours) post-T cell activation, after which MSCs can no longer exert their immunoregulatory capacity...
2017: PloS One
https://www.readbyqxmd.com/read/28073842/expression-of-cd14-il-10-and-tolerogenic-signature-in-dendritic-cells-inversely-correlate-with-response-to-tarp-vaccination-in-prostate-cancer-patients
#8
Luciano Castiello, Marianna Sabatino, Jiaqiang Ren, Masaki Terabe, Hanh Khuu, Lauren V Wood, Jay A Berzofsky, David F Stroncek
PURPOSE: Despite the vast number of clinical trials conducted so far, Dendritic cell (DC)-based cancer vaccines have mostly shown unsatisfactory results. Factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. We here aimed to identify DC markers correlating with clinical and immunological response in a prostate carcinoma vaccination regimen. EXPERIMENTAL DESIGN: We performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258)...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#9
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28063891/gm-csf-and-il-4-produced-by-nkt-cells-inversely-regulate-il-1%C3%AE-production-by-macrophages
#10
Sehee Ahn, Dongjin Jeong, Sae Jin Oh, Jiye Ahn, Seung Hyo Lee, Doo Hyun Chung
Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production...
January 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28060873/assessment-of-anterior-cingulate-cortex-acc-and-left-cerebellar-metabolism-in-asperger-s-syndrome-with-proton-magnetic-resonance-spectroscopy-mrs
#11
Aya Goji, Hiromichi Ito, Kenji Mori, Masafumi Harada, Sonoka Hisaoka, Yoshihiro Toda, Tatsuo Mori, Yoko Abe, Masahito Miyazaki, Shoji Kagami
PURPOSE: Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear...
2017: PloS One
https://www.readbyqxmd.com/read/28054639/rapid-recall-ability-of-memory-t-cells-is-encoded-in-their-epigenome
#12
Artem Barski, Suresh Cuddapah, Andrey V Kartashov, Chong Liu, Hiromi Imamichi, Wenjing Yang, Weiqun Peng, H Clifford Lane, Keji Zhao
Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053236/cd8-t-cells-that-coexpress-ror%C3%AE-t-and-t-bet-are-functionally-impaired-and-expand-in-patients-with-distal-bile-duct-cancer
#13
Stalin Chellappa, Harald Hugenschmidt, Morten Hagness, Saranya Subramani, Espen Melum, Pål Dag Line, Knut-Jørgen Labori, Gro Wiedswang, Kjetil Taskén, Einar Martin Aandahl
CD8(+) T cells that express retinoic acid-related orphan receptor (ROR)γt (TC17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8(+)RORγt(+) T cells (TC17 cells) was increased in peripheral blood. The CD8(+)RORγt(+) T cells represented a highly activated subset and produced IL-17A in equal amount as CD4(+)RORγt(+) T cells (TH17 cells)...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28053234/tcr-signaling-and-cd28-ctla-4-signaling-cooperatively-modulate-t-regulatory-cell-homeostasis
#14
Michael P Holt, George A Punkosdy, Deborah D Glass, Ethan M Shevach
Foxp3(+) T regulatory cells (Tregs), conventional CD4(+)Foxp3(-) T cells, and CD8(+) T cells represent heterogeneous populations composed of naive phenotype (NP, CD44(low)) and memory phenotype (MP, CD44(high)) subpopulations. NP and MP subsets differ in their activation state, contribution to immune function, and capacity to proliferate in vivo. To further understand the factors that contribute to the differential homeostasis of NP/MP subsets, we examined the differential effects of CD28 and CTLA-4 interaction with CD80/CD86, as well as MHC class II-TCR interaction within mouse Treg pools and CD4(+) and CD8(+) T cell pools...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28052935/d120-and-k152-within-the-ph-domain-of-t-cell-adapter-skap55-regulate-plasma-membrane-targeting-of-skap55-and-lfa-1-affinity-modulation-in-human-t-lymphocytes
#15
Amelie Witte, Bernhard Meineke, Jana Sticht, Lars Philipsen, Benno Kuropka, Andreas J Müller, Christian Freund, Burkhart Schraven, Stefanie Kliche
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for T cell receptor (TCR) induced activation of LFA-1 to promote T cell adhesion and interaction with antigen presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src Kinase-Associated Phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its Pleckstrin Homology (PH) domain...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#16
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28050271/evolution-of-tumor-clones-in-adult-acute-lymphoblastic-leukemia
#17
S Yu Smirnova, Yu V Sidorova, N V Ryzhikova, K A Sychevskaya, E N Parovichnikova, A B Sudarikov
Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonal TCR and IG genes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28045060/soluble-ox40l-and-jag1-induce-selective-proliferation-of-functional-regulatory-t-cells-independent-of-canonical-tcr-signaling
#18
Prabhakaran Kumar, Khaled Alharshawi, Palash Bhattacharya, Alejandra Marinelarena, Christine Haddad, Zuoming Sun, Shigeru Chiba, Alan L Epstein, Bellur S Prabhakar
Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28030587/cd5-ck2-signaling-modulates-erk-activation-and-thymocyte-survival
#19
Carlos A Mier-Aguilar, Kevin S Cashman, Chander Raman, Gloria Soldevila
CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#20
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
December 27, 2016: Aging Cell
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