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https://www.readbyqxmd.com/read/29128554/immunomodulatory-effects-of-tyrosine-kinase-inhibitors-tkis-in-vitro-and-in-vivo-study
#1
Elena Marinelli Busilacchi, Andrea Costantini, Nadia Viola, Benedetta Costantini, Jacopo Olivieri, Luca Butini, Giorgia Mancini, Ilaria Scortechini, Martina Chiarucci, Monica Poiani, Antonella Poloni, Pietro Leoni, Attilio Olivieri
Pathogenesis of chronic Graft Versus Host Disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes, as well as B cells. Standard treatment is lacking for steroid dependent/refractory cases; potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent anti-fibrotic effect. However, TKI seems to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29103633/cd8-cd28-cd127-lo-cd39-regulatory-t-cell-expansion-a%C3%A2-new-possible-pathogenic-mechanism-for-hiv-infection
#2
Daniela Fenoglio, Chiara Dentone, Alessio Signori, Antonio Di Biagio, Alessia Parodi, Francesca Kalli, Giorgia Nasi, Monica Curto, Giovanni Cenderello, Pasqualina De Leo, Valentina Bartolacci, Giancarlo Orofino, Laura Ambra Nicolini, Lucia Taramasso, Edoardo Fiorillo, Valeria Orrù, Paolo Traverso, Bianca Bruzzone, Federico Ivaldi, Eugenio Mantia, Michele Guerra, Simone Negrini, Mauro Giacomini, Sanjay Bhagani, Gilberto Filaci
BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4(+) T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4(+) T cells/μL. CD8(+)CD28(-)CD127(lo)CD39(+) T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8(+)CD28(-)CD127(lo)CD39(+) Treg cells in the circulation of HIV-infected patients...
October 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#3
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#4
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29075318/t-and-nk-cell-populations-with-regulatory-phenotype-and-markers-of-apoptosis-in-circulating-lymphocytes-of-patients-with-cin3-or-microcarcinoma-of-the-cervix-evidence-for-potential-mechanisms-of-immune-suppression
#5
Olga V Kurmyshkina, Pavel I Kovchur, Ludmila V Schegoleva, Tatyana O Volkova
BACKGROUND: Processes and mechanisms responsible for systemic immune suppression in early-stage cervical cancer remain substantially underinvestigated. In this work, we focused on studying the frequencies of circulating regulatory T (CD4 and CD8 Tregs) and NK (NKregs) cells in parallel with assessment of apoptotic markers expression in T cells from patients with preinvasive and microinvasive cervical cancer, with the aim to determine whether up-regulation of apoptosis-associated markers in Т lymphocytes accompanies cervical cancer development and correlates with the change in percentages of regulatory cell populations at systemic level during the initial stages of invasive cervical cancer progression...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29070122/-levels-of-t-lymphocyte-subsets-il-17-il-35-and-ifn-%C3%AE-in-peripheral-blood-and-their-clinical-significance-in-patients-with-multiple-myeloma
#6
Zhao-Juan Xu, Dong Zhao, Fu-Ping Li, Ying-Fang Wang, Hui-Ying Xiao, Xu Wang
OBJECTIVE: To explore the levels of T-lymphocyte subsets and IL-17, IL-35, IFN-γ in peripheral blood of patients with multiple myeloma(MM) and their clinical significance. METHODS: A total of 86 MM patients in our hospital from January 2014 to January 2017 were enrolled in MM group and 30 healthy persons were enrolled in control group, the CD4(+)/CD8(+) T cells ratio, CD4(+)CD25(high/+) CD127(low/-) Treg level in peripheral blood were detected by flow cytometer...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29057512/induction-of-porcine-specific-regulatory-t-cells-with-high-specificity-and-expression-of-il-10-and-tgf-%C3%AE-1-using-baboon-derived-tolerogenic-dendritic-cells
#7
Mingqian Li, Judith Eckl, Jan-Michael Abicht, Tanja Mayr, Bruno Reichart, Dolores J Schendel, Heike Pohla
BACKGROUND: Regulatory T cells (Treg) play an important role in maintenance of homeostasis in vivo. Treg application to alleviate allo-organ rejection is being studied extensively. However, natural Treg (nTreg) expansion in vitro is laborious and expensive. Antigen-specific Treg are more effective and require lower cell numbers than use of nTreg for immune control. The baboon, as a non-human primate experimental animal model, is widely used in xenotransplantation research. An effective method to generate baboon xeno-specific Treg would benefit research on immune tolerance in xenotransplantation using this model system...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29056444/long-lived-tissue-resident-hiv-1-specific-memory-cd8-t-cells-are-generated-by-skin-immunization-with-live-virus-vectored-microneedle-arrays
#8
Marija Zaric, Pablo Daniel Becker, Catherine Hervouet, Petya Kalcheva, Barbara Ibarzo Yus, Clement Cocita, Lauren Alexandra O'Neill, Sung-Yun Kwon, Linda Sylvia Klavinskis
The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin...
October 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29054723/aberrant-frequency-of-il-35-producing-b-cells-in-colorectal-cancer-patients
#9
Ke Wang, Hui Gong, Rui Chai, Hang Yuan, Yanxia Chen, Jinlin Liu
BACKGROUND: The IL-10 dependent regulatory function of B cells had recently more and more investigated and play important roles in cancer immunity, however, beyond IL-10 whether other inhibitory cytokines play an important role in cancer is lacking. Here, we investigated the role of IL-35 producing B cells in colorectal cancer (CRC). METHODS: Thirty-two healthy controls (HC) and 49 untreated CRC patients were enrolled and the IL-35 producing B cells in the peripheral blood were investigated...
October 17, 2017: Cytokine
https://www.readbyqxmd.com/read/29045900/molecular-and-functional-characterization-of-lymphoid-progenitor-subsets-reveals-a-bipartite-architecture-of-human-lymphopoiesis
#10
Kutaiba Alhaj Hussen, Thien-Phong Vu Manh, Fabien Guimiot, Elisabeth Nelson, Emna Chabaane, Marc Delord, Maxime Barbier, Claire Berthault, Nicolas Dulphy, Antonio José Alberdi, Odile Burlen-Defranoux, Gerard Socié, Jean Christophe Bories, Jerôme Larghero, Valérie Vanneaux, Els Verhoeyen, Thierry Wirth, Marc Dalod, Jean Claude Gluckman, Ana Cumano, Bruno Canque
The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#11
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29023682/short-term-cytokine-stimulation-reveals-regulatory-t%C3%A2-cells-with-down-regulated-foxp3-expression-in-human-peripheral-blood
#12
Paula Tabares, Susanne Berr, Daniela Langenhorst, Birgit Sawitzki, Ineke Ten Berge, Hans-Peter Tony, Thomas Hünig
The identification of regulatory T cells (Treg cells) in human peripheral blood is an important tool in diagnosis, research, and therapeutic intervention. As compared to lymphoid tissues, the frequencies of circulating Treg cells identified as CD4(+) CD25(+) Foxp3(+) are, however, low. We here show that many of these cells remain undetected due to transient down regulation of Foxp3, which rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term incubation of PBMCs or isolated CD4(+) T cells, but not of lymph node cells, with IL-2, -7, or -15 more than doubles the frequency of Foxp3(+) CD25(+) among CD4(+) T cells detectable by flow cytometry...
October 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#13
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28973925/foxo1-opposition-of-cd8-t-cell-effector-programming-confers-early-memory-properties-and-phenotypic-diversity
#14
Arnaud Delpoux, Chen-Yen Lai, Stephen M Hedrick, Andrew L Doedens
The factors and steps controlling postinfection CD8(+) T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8(+) T cells. We determined the early postinfection TCF7(high) population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R)...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28955342/mass-cytometry-identifies-distinct-lung-cd4-t-cell-patterns-in-l%C3%A3-fgren-s-syndrome-and-non-l%C3%A3-fgren-s-syndrome-sarcoidosis
#15
Ylva Kaiser, Tadepally Lakshmikanth, Yang Chen, Jaromir Mikes, Anders Eklund, Petter Brodin, Adnane Achour, Johan Grunewald
Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4(+) T cells in the lungs. Disease phenotypes Löfgren's syndrome (LS) and "non-LS" differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03(+) LS and four HLA-DRB1*03(-) non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28951703/cutaneous-leukocytoclastic-vasculitis-the-role-of-lymphocytes-and-related-immune-markers
#16
Thilo Gambichler, Magdalena A Kulik, Marina Skrygan, Isabelle Rooms, Stefan Höxtermann
INTRODUCTION: Apart from neutrophils, other immune cells may play a significant pathogenetic role in cutaneous leukocytoclastic vasculitis (CLV). AIM: To investigate lymphocytes and related immunological factors in patients with CLV requiring systemic glucocorticosteroid treatment. MATERIAL AND METHODS: Fourteen patients with severe idiopathic CLV were treated with systemic prednisolone in a tapered dose regimen. Ten healthy individuals served as controls...
August 2017: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28941291/dysregulation-of-circulating-tfr-tfh-ratio-in-primary-biliary-cholangitis
#17
Jiajia Zheng, Tiancheng Wang, Li Zhang, Liyan Cui
Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are critical for the development and maintenance of germinal center (GC) and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh cells or Tfr cells contributes to the pathogenesis of autoimmune diseases. We aim to investigate the roles of circulating Tfh cells and circulating Tfr cells in the pathogenesis of primary biliary cholangitis (PBC). 34 PBC patients and 27 health individuals were enrolled in this study...
September 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#18
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#19
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28912776/human-cd5-innate-lymphoid-cells-are-functionally-immature-and-their-development-from-cd34-progenitor-cells-is-regulated-by-id2
#20
Maho Nagasawa, Kristine Germar, Bianca Blom, Hergen Spits
Innate lymphoid cells (ILCs) have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2) for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF), and maintained CD127 expression, markers that are characteristic for human ILCs...
2017: Frontiers in Immunology
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