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https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#1
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28225764/cynomolgus-macaques-naturally-infected-with-trypanosoma-cruzi-i-exhibit-an-overall-mixed-pro-inflammatory-modulated-cytokine-signature-characteristic-of-human-chagas-disease
#2
Danielle Marquete Vitelli-Avelar, Renato Sathler-Avelar, Armanda Moreira Mattoso-Barbosa, Nicolas Gouin, Marcelo Perdigão-de-Oliveira, Leydiane Valério-Dos-Reis, Ronaldo Peres Costa, Silvana Maria Elói-Santos, Matheus de Souza Gomes, Laurence Rodrigues do Amaral, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Edward J Dick, Gene B Hubbard, Jane F VandeBerg, John L VandeBerg
BACKGROUND: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28225449/ifn-%C3%AE-augments-natural-killer-mediated-antibody-dependent-cellular-cytotoxicity-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-major-histocompatibility-complex-class-1-downregulation
#3
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
March 13, 2017: AIDS
https://www.readbyqxmd.com/read/28225293/rituximab-associated-progressive-multifocal-leukoencephalopathy
#4
Juraj Sokol, Lenka Lisá, Jana Zeleňáková, Tomáš Balhárek, Ivana Plameňová, Ján Staško, Peter Kubisz
The definition "Progressive Multifocal Leukoencephalopathy" (PML) was first used in 1958 to describe a fatal demyelinating central nervous system (CNS) disease in patients with lymphoproliferative disorders. In 1971, the virus responsible for the disease was isolated and named John Cunningham virus (JCV). We present a rare case of a 62-year-old male with chronic lymphocytic leukemia and PML. In our work, we discuss the diagnostic and therapeutic challenges and offer suggestions for preventing PML development...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28224733/nk1-1-cd4-nkg2d-t-cells-suppress-dss-induced-colitis-in-mice-through-production-of-tgf-%C3%AE
#5
Xingxing Qian, Chunxia Hu, Sen Han, Zhijie Lin, Weiming Xiao, Yanbing Ding, Yu Zhang, Li Qian, Xiaoqing Jia, Guoqiang Zhu, Weijuan Gong
CD4(+) NKG2D(+) T cells are associated with tumour, infection and autoimmune diseases. Some CD4(+) NKG2D(+) T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4(+) NKG2D(+) T cells were further classified into NK1.1(-) CD4(+) NKG2D(+) and NK1.1(+) CD4(+) NKG2D(+) subpopulations. The frequency of NK1.1(-) CD4(+) NKG2D(+) cells decreased in inflamed colons, whereas more NK1.1(+) CD4(+) NKG2D(+) cells infiltrated into colons of mice with DSS-induced colitis...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28224362/analysis-of-foxp3-regulatory-t-cell-subpopulations-in-peripheral-blood-and-tissue-of-patients-with-systemic-lupus-erythematosus
#6
Angelika Schmidt, Cosima C Rieger, Ram Kumar Venigalla, Szabolcs Éliás, Regina Max, Hanns-Martin Lorenz, Hermann-Josef Gröne, Peter H Krammer, Annegret Kuhn
Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4(+) T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry...
February 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28224222/immunopathological-characterization-of-human-cutaneous-leishmaniasis-lesions-caused-by-leishmania-viannia-spp-in-amazonian-brazil
#7
Cláudia Maria Castro Gomes, Maria Gloria Teixeira Sousa, Joyce Prieto Bezerra Menezes, Marliane Campos Batista, Ana Carolina Stocco Lima, Walter Belda, Daniel Bradshaw, Monica Elinor Alves Gama, Márcia Dalastra Laurenti, Fernando Tobias Silveira, Carlos Eduardo Pereira Corbett
American cutaneous leishmaniasis (ACL) is a chronic infectious disease caused by different protozoan species of Leishmania, and it is endemic in both tropical and subtropical countries. Using immunohistochemistry, we investigate the density of CD68(+), lysozyme(+), CD1a(+), factor XIIIa(+), CD4(+), CD8(+), CD56(+), interferon (IFN)-γ(+), and inducible NO synthase (iNOS(+)) cells. These cells were analyzed from 22 biopsy samples obtained from the lesions of ACL patients, whose infection was caused by Leishmania (Viannia) spp...
February 21, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28223987/dendritic-cell-targeting-effectively-boosts-t-cell-responses-elicited-by-an-hiv-multiepitope-dna-vaccine
#8
Juliana de Souza Apostólico, Victória Alves Santos Lunardelli, Marcio Massao Yamamoto, Higo Fernando Santos Souza, Edecio Cunha-Neto, Silvia Beatriz Boscardin, Daniela Santoro Rosa
Despite several efforts in the last decades, an efficacious HIV-1 vaccine is still not available. Different approaches have been evaluated, such as recombinant proteins, viral vectors, DNA vaccines, and, most recently, dendritic cell (DC) targeting. This strategy is based on DC features that place them as central for induction of immunity. Targeting is accomplished by the use of chimeric monoclonal antibodies directed to DC surface receptors fused to the antigen of interest. In this work, we targeted eight promiscuous HIV-derived CD4(+) T cell epitopes (HIVBr8) to the DEC205(+) DCs by fusing the multiepitope immunogen to the heavy chain of αDEC205 (αDECHIVBr8), in the presence of the TLR3 agonist poly (I:C)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223983/b-cell-homeostasis-and-functional-properties-are-altered-in-an-hypochlorous-acid-induced-murine-model-of-systemic-sclerosis
#9
Sébastien Sanges, Manel Jendoubi, Niloufar Kavian, Carine Hauspie, Silvia Speca, Jean-Charles Crave, Thomas Guerrier, Guillaume Lefèvre, Vincent Sobanski, Ariel Savina, Eric Hachulla, Pierre-Yves Hatron, Myriam Labalette, Frédéric Batteux, Sylvain Dubucquoi, David Launay
INTRODUCTION: During systemic sclerosis (SSc), peripheral B cells display alterations in subset homeostasis and functional properties and are a promising therapeutic target. However, there is only few data regarding whether these anomalies are accurately reproduced in animal models of SSc. OBJECTIVE: In this work, we assessed the B cell homeostasis modifications in an experimental model of SSc [hypochlorous acid (HOCl)-induced mouse], both at a phenotypic and functional level, during the course of the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223815/antitumor-effects-of-oncolytic-herpes-simplex-virus-type-2-against-colorectal-cancer-in-vitro-and-in-vivo
#10
Lei Yin, Chunhong Zhao, Jixia Han, Zengjun Li, Yanan Zhen, Ruixue Xiao, Zhongfa Xu, Yanlai Sun
BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28223726/dendritic-cells-engineered-to-secrete-anti-dcr3-antibody-augment-cytotoxic-t-lymphocyte-response-against-pancreatic-cancer-in-vitro
#11
Jiang Chen, Xiao-Zhong Guo, Hong-Yu Li, Jia-Jun Zhao, Wen-Da Xu
AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#12
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223351/in-vivo-and-in-vitro-proteome-analysis-of-hiv-1-infected-human-cd4-t-cells
#13
Johannes Nemeth, Valentina Vongrad, Karin J Metzner, Victoria Strouvelle, Rainer Weber, Patrick Pedrioli, Ruedi Aebersold, Huldrych Guenthard, Ben C Collins
Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28222797/melanoma-antigen-specific-effector-t-cell-cytokine-secretion-patterns-in-patients-treated-with-ipilimumab
#14
Yana G Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4(+) and CD8(+) T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222785/tcd4-pos-lymphocytosis-in-rheumatoid-and-psoriatic-arthritis-patients-following-tnf%C3%AE-blocking-agents
#15
Andrea Picchianti Diamanti, Bruno Laganà, Maria Christina Cox, Emanuela Pilozzi, Rachele Amodeo, Maurizio Bove, Milica Markovic, Roberta Di Rosa, Simonetta Salemi, Maria Laura Sorgi, Maria Manuela Rosado, Raffaele D'Amelio
BACKGROUND: Lymphocyte expansion and true lymphocytosis are commonly observed in the everyday clinical practice. The meaning of such phenomenon is often poorly understood so that discrimination between benign and malignant lymphocytosis remains difficult to establish. This is mainly true when lymphocytosis rises in patients affected by immune-mediated chronic inflammatory diseases under immunosuppressive treatment, conditions potentially associated with lymphomagenesis. In this brief report the development of mild T CD4(pos) lymphocytosis in a group of patients with chronic arthritis under anti-TNF-α treatment is described...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222782/identification-of-mirna-mrna-crosstalk-in-cd4-t-cells-during-hiv-1-infection-by-integrating-transcriptome-analyses
#16
Qibin Liao, Jin Wang, Zenglin Pei, Jianqing Xu, Xiaoyan Zhang
BACKGROUND: HIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7-10 years, but keeping high CD4(+) T cell counts and low viral load in the absence of antiretroviral treatment, while loss of CD4(+) T cells and high viral load were observed in the most of HIV-1-infected individuals with chronic progressors (CPs) However, the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved. METHODS: To identify microRNAs (miRNAs) and their target genes related to distinct clinical outcomes in HIV-1 infection, we performed the integrative transcriptome analyses in two series GSE24022 and GSE6740 by GEO2R, R, TargetScan, miRDB, and Cytoscape softwares...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222702/the-virological-durability-of-first-line-art-among-hiv-positive-adult-patients-in-resource-limited-settings-without-virological-monitoring-a-retrospective-analysis-of-dart-trial-data
#17
David I Dolling, Ruth L Goodall, Michael Chirara, James Hakim, Peter Nkurunziza, Paula Munderi, David Eram, Dinah Tumukunde, Moira J Spyer, Charles F Gilks, Pontiano Kaleebu, David T Dunn, Deenan Pillay
BACKGROUND: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. METHODS: DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling...
February 21, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28222462/decreased-frequencies-of-peripheral-blood-cd4-cd25-cd127-foxp3-in-patients-with-graves-disease-and-graves-orbitopathy-enhancing-effect-of-insulin-growth-factor-1-on-treg-cells
#18
Przemyslaw Pawlowski, Kamil Grubczak, Jerzy Kostecki, Elzbieta Ilendo-Poskrobko, Marcin Moniuszko, Malgorzata Pawlowska, Robert Rejdak, Joanna Reszec, Janusz Mysliwiec
Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127(-), Foxp3) on T cells and their ability to respond to IGF-1 stimulation...
February 21, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28222146/cytotoxic-effector-functions-of-t-cells-are-not-required-for-protective-immunity-against-fatal-rickettsia-typhi-infection-in-a-murine-model-of-infection-role-of-th1-and-th17-cytokines-in-protection-and-pathology
#19
Kristin Moderzynski, Liza Heine, Jessica Rauch, Stefanie Papp, Svenja Kuehl, Ulricke Richardt, Bernhard Fleischer, Anke Osterloh
Endemic typhus caused by Rickettsia (R.) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for protection against R. typhi by T cells in the CB17 SCID model of infection. BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD8+ T cells both of which are sporadically reactivated in persistent infection. Either adoptively transferred CD8+ or CD4+ T cells protected R. typhi-infected CB17 SCID mice from death and provided long-term control...
February 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28222098/multicenter-study-of-skin-rashes-and-hepatotoxicity-in-antiretroviral-na%C3%A3-ve-hiv-positive-patients-receiving-non-nucleoside-reverse-transcriptase-inhibitor-plus-nucleoside-reverse-transcriptase-inhibitors-in-taiwan
#20
Pei-Ying Wu, Chien-Yu Cheng, Chun-Eng Liu, Yi-Chien Lee, Chia-Jui Yang, Mao-Song Tsai, Shu-Hsing Cheng, Shih-Ping Lin, De-Yu Lin, Ning-Chi Wang, Yi-Chieh Lee, Hsin-Yun Sun, Hung-Jen Tang, Chien-Ching Hung
OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study...
2017: PloS One
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