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Dallas Jones, Christina N Como, Lichen Jing, Anna Blackmon, Charles Preston Neff, Owen Krueger, Andrew N Bubak, Brent E Palmer, David M Koelle, Maria A Nagel
Varicella zoster virus (VZV) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster, vascular disease and vision loss upon reactivation from latency. VZV-infected peripheral blood mononuclear cells (PBMCs) disseminate virus to distal organs to produce clinical disease. To assess immune evasion strategies elicited by VZV that may contribute to dissemination of infection, human PBMCs and VZV-specific CD8+ T cells (V-CD8+) were mock- or VZV-infected and analyzed for immunoinhibitory protein PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression using flow cytometry...
March 14, 2019: PLoS Pathogens
Qing Zhao, Khetam Alhilali, Abdulaziz Alzahrani, Mubarak Almutairi, Juwaria Amjad, Hong Liu, Yonghu Sun, Lele Sun, Huimin Zhang, Xiaoli Meng, Andrew Gibson, Monday O Ogese, B Kevin Park, Jianjun Liu, David A Ostrov, Furen Zhang, Dean J Naisbitt
BACKGROUND: Research into drug hypersensitivity associated with expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, we have studied HLA-B*13:01-linked dapsone hypersensitivity to (1) explore whether the parent drug and/or nitroso metabolite activates T-cells and (2) determine whether HLA-B*13:01 is involved in the response. METHODS: PBMC from 6 patients were cultured with dapsone and nitroso dapsone and proliferative responses and IFN-γ release were measured...
March 7, 2019: Allergy
Jayaum S Booth, Eric Goldberg, Seema A Patil, Bruce D Greenwald, Marcelo B Sztein
CD4+ and CD8+ T subsets are essential components of the adaptive immune system which act in concert at the site of infections to effectively protect against pathogens. Very limited data is available in humans regarding the relationship between CD4+ and CD8+ S. Typhi responsive cells in the terminal ileum mucosa (TI) and peripheral blood following Ty21a oral typhoid immunization. Here, we compared TI lamina propria mononuclear cells (LPMC) and peripheral blood CD4+ and CD8+ T memory (TM ) subsets responses and their relationship by Spearman's correlation following Ty21a immunization in volunteers undergoing routine colonoscopy...
March 6, 2019: Human Vaccines & Immunotherapeutics
Thaysse Ferreira Leite, Edson Delatorre, Fernanda Heloise Côrtes, Ana Cristina Garcia Ferreira, Sandra Wagner Cardoso, Beatriz Grinsztejn, Michelle Morata de Andrade, Valdilea Gonçalves Veloso, Mariza Gonçalves Morgado, Monick Lindenmeyer Guimarães
The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART ) and 12 months (M12ART ) after suppressive cART...
2019: Frontiers in Microbiology
Geoffrey C Owens, Alejandro J Garcia, Aaron Y Mochizuki, Julia W Chang, Samuel D Reyes, Noriko Salamon, Robert M Prins, Gary W Mathern, Aria Fallah
Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) ( n = 1), Tuberous sclerosis complex (TSC) ( n = 2), Focal cortical dysplasia (FCD) ( n = 4), and Rasmussen encephalitis (RE) ( n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set...
2019: Frontiers in Immunology
Mingkui Zhou, Michael Humbert, Muhammad M Mukhtar, Hanna B Scinto, Hemant K Vyas, Samir K Lakhashe, Siddappa N Byrareddy, Gregor Maurer, Swati Thorat, Joshua Owuor, Zhao Lai, Yidong Chen, Anthony Griffiths, Agnès-Laurence Chenine, Sanjeev Gumber, François Villinger, David Montefiori, Ruth M Ruprecht
Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of Africa. We constructed an R5 clade A SHIV (SHIV-A; strain SHIV-KNH1144) carrying env from a Kenyan HIV-A. SHIV-A underwent rapid serial passage through six RMs. To allow unbridled replication without adaptive immunity, we simultaneously ablated CD8+ and B cells with cytotoxic monoclonal antibodies in the next RM, resulting in extremely high viremia and CD4+ T-cell loss...
February 13, 2019: Journal of Virology
S Wojnicki, A Morris, B N Smith, C W Maddox, R N Dilger
An experiment was conducted to evaluate growth performance, fecal bacterial counts, frequency of diarrhea, and clinical blood parameters in weanling pigs inoculated with enterotoxigenic Escherichia coli (ETEC) who were fed a whole yeast cell (WYC) product and capsicum, a plant essential oil. Weanling pigs (34 barrows and 30 gilts, 21 d of age, 5.90 ± 1.03 kg BW) were allotted to experimental treatments in a randomized complete block design based on litter, sex, and initial BW. Four pigs were individually housed within each containment chamber and assigned to 1 of 4 dietary treatments, which included a control diet without or with 0...
February 11, 2019: Journal of Animal Science
Kenneth A Fowler, Viktoria Vasilieva, Ekaterina Ivanova, Olga Rimkevich, Andrey Sokolov, Svetlana Abbasova, Eldar Kim, James M Coghill
Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation (HSCT). Previously, we demonstrated that CC-Chemokine Receptor 7 (CCR7) is critical for aGVHD pathogenesis but dispensable for beneficial graft-versus-leukemia (GVL) responses. As a result, we evaluated a fully human anti-CCR7 blocking antibody as a new approach to prevent aGVHD in preclinical models. Here we report that antibody R707 is able to block human CCR7 signaling and function in vitro in response to its two natural ligands...
February 12, 2019: American Journal of Transplantation
Collin Richard Diedrich, Hannah Priyadarshini Gideon, Tara Rutledge, Tonilynn Marie Baranowski, Pauline Maiello, Amy J Myers, Philana Ling Lin
BACKGROUND: Tuberculosis (TB) kills millions of people every year. CD4 and CD8 T cells are critical in the immune response against TB. T cells expressing both CD4 and CD8 (CD4CD8 T cells) are functionally active and have not been examined in the context of TB. METHODS: We examine peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage cells (BAL) and lung granulomas from 28 cynomolgus macaques during Mycobacterium tuberculosis (Mtb) infection. RESULTS: CD4CD8 T cells increase in frequency during early Mtb infection in PBMC and BAL from pre-infection...
February 5, 2019: Journal of Medical Primatology
Pascal Ickrath, Agmal Scherzad, Norbert Kleinsasser, Chr Ginzkey, Rudolf Hagen, Stephan Hackenberg
T cell subpopulations in nasal polyps differ from peripheral lymphocytes in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, little is known about the modulatory influence of the inflamed nasal polyp epithelial cells on the phenotype of the T cells. The aim of the present study was to assess this interaction. Tissue and blood samples were collected from 16 patients undergoing paranasal sinus surgery. Polypoid tissue was cultured under air-liquid interface conditions. Subsequently, cluster of differentiation (CD)3/CD28 activated peripheral lymphocytes from the same patients were added...
February 2019: Biomedical Reports
Xining Yang, Ning Kang, Wendy M Toyofuku, Mark D Scott
T lymphocytes play a critical role in the pro-inflammatory anti-cancer response; hence, significant pharmacologic efforts have been made to enhance the endogenous T cell response. Unfortunately, significant toxicity arises consequent to pan T cell activation. In contrast, the less robust T cell alloresponse has also demonstrated an anti-cancer effect, but poses an inherent risk of GvHD. To overcome the GvHD risk, an acellular pro-inflammatory agent (IA1) has been biomanufactured from the secretome of the allorecognition response...
December 28, 2018: Immunobiology
Sharon Witonsky, Virginia Buechner-Maxwell, Amy Santonastasto, Robert Pleasant, Stephen Werre, Bettina Wagner, Siobhan Ellison, David Lindsay
BACKGROUND: Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM-affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses. OBJECTIVE: Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T-helper 1 (CD4 Th1), and T-cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro as compared to mitogen alone...
January 29, 2019: Journal of Veterinary Internal Medicine
David Agdashian, Mei ElGindi, Changqing Xie, Milan Sandhu, Drew Pratt, David E Kleiner, William D Figg, Julie A Rytlewski, Catherine Sanders, Erik C Yusko, Bradford Wood, David Venzon, Gagandeep Brar, Austin G Duffy, Tim F Greten, Firouzeh Korangy
BACKGROUND: Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%. METHODS: Here, we report updated survival analyses and results from our immune monitoring studies on peripheral blood mononuclear cells (PBMCs) and tumors from these patients...
January 28, 2019: Cancer Immunology, Immunotherapy: CII
John K Bui, Joshua C Cyktor, Elizabeth Fyne, Shalyn Campellone, Stephen W Mason, John W Mellors
Blockade of the programmed cell death protein/ligand 1 (PD-1/PD-L1) pathway with monoclonal antibodies (mAb) is now commonly used for cancer immunotherapy and has therapeutic potential in chronic viral infections including HIV-1. PD-1/PD-L1 blockade could augment HIV-1-specific immune responses and reverse HIV-1 latency, but the latter effect has not been clearly shown. We tested the ability of the human anti-PD-L1 mAb BMS-936559 and the human anti-PD-1 mAb nivolumab to increase HIV-1 virion production ex vivo from different peripheral blood mononuclear cell populations obtained from donors on suppressive antiretroviral therapy (ART)...
2019: PloS One
Khetam Ali Alhilali, Zaid Al-Attar, Andrew Gibson, Arun Tailor, Xiaoli Meng, Mario Monshouwer, Jan Snoeys, B Kevin Park, Dean J Naisbitt
Telaprevir, a protease inhibitor, was used alongside PEGylated interferon-α and ribavirin to treat hepatitis C viral infections. The triple regimen proved successful; however, the appearance of severe skin reactions alongside competition from newer drugs restricted its use. Skin reactions presented with a delayed onset indicative of a T-cell mediated reaction. Thus, the aim of this study was to investigate whether telaprevir and/or its diastereomer, which is generated in humans, activates T-cells. Telaprevir in its S-configured therapeutic form and the R-diastereomer were cultured directly with PBMC from healthy donors prior to the generation of T-cell clones by serial dilution...
January 12, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
Brie M Reid, Christopher L Coe, Colleen M Doyle, Dagna Sheerar, Alla Slukvina, Bonny Donzella, Megan R Gunnar
The developing immune system is an adaptive system, primed by antigens, responsive to infectious pathogens, and can be affected by other aspects of the early rearing environment, including deviations from the normal provision of parental care. We investigated whether early rearing in an institutional setting, even when followed by years living in supportive and well-resourced families, would be associated with a persistent shift in T cell profiles. Immunophenotyping was used to enumerate CD4+CD57+ and CD8+CD57+ subsets, with gating strategies employed to differentiate naïve, central-memory, effector-memory, and terminally differentiated EM cells expressing CD45RA (TEMRA)...
January 9, 2019: Brain, Behavior, and Immunity
Qiang Zeng, Xiao-Ye Yuan, Wei Li, Bao-Wang Liu, Xin Zhao, Gui-Jun Ren, Yang Wang, Jian Dou, Gui-Ying Wang
CONTEXT: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients. OBJECTIVE: In this study, we detected the effects of FK506 and MMF on the expressions of regulatory T cells (Tregs) and co-inhibitory receptors on Tregs in peripheral blood mononuclear cells (PBMC) of patients with stable phase after liver transplantation. MATERIALS AND METHODS: A total of 35 patients with stable stage after 6 months of liver transplantation were divided into two groups including 20 patients were treated with FK506 monotherapy (FK506 group), and 15 patients with FK506 and MMF combination (FK506 + MMF group)...
January 11, 2019: Immunopharmacology and Immunotoxicology
Gabriella D'ettorre, Cristian Borrazzo, Claudia Pinacchio, Letizia Santinelli, Eugenio N Cavallari, Maura Statzu, Gianfranco Fanello, Giancarlo Ceccarelli, Guido Antonelli, Vincenzo Vullo, Claudio M Mastroianni, Carolina Scagnolari
OBJECTIVE: The influence of gender on gut mucosal T cell response in HIV-1 infection remains largely unknown. We explored whether the frequencies of IFN-[Latin Small Letter Gamma] and/or IL-17 producing naïve, central (TCM) and effector (TEM) memory CD4+ (Th1, Th17) and CD8+ T (Tc1, Tc17) cells measured in gut and peripheral districts differed between female and male HIV-1-infected patients. METHODS: Thirty long-term treated HIV-infected individuals were enrolled...
January 2, 2019: AIDS
Luca Bertero, Sarah Beth Joseph, Mattia Trunfio, Tiziano Allice, Sebastiano Catera, Daniele Imperiale, Paola Cassoni, Laura Pesci Kincer, Veronica Pirriatore, Valeria Ghisetti, Enrica Amasio, Gianluigi Zanusso, Stefano Bonora, Giovanni Di Perri, Andrea Calcagno
OBJECTIVE: Human Immunodeficiency virus (HIV) infection chronically affects the central nervous system (CNS). Olfactory mucosa (OM) is a unique site in the respiratory tract that is directly connected to the CNS, thus we wanted to evaluate OM as a surrogate of CNS sampling. DESIGN: We conducted a preliminary study examining HIV populations and susceptible cells in the OM. METHODS: OM was sampled by minimally invasive brushing. CSF analyses were performed as per routine clinical procedures...
January 2, 2019: AIDS
Christiane L Schnabel, Michelle Wemette, Susanna Babasyan, Heather Freer, Cynthia Baldwin, Bettina Wagner
Chemokines are soluble molecules directing immune cell trafficking and homing, mediating inflammation, and initiating immune responses to infection. In horses, the analysis of chemokines has been limited by the lack of specific antibodies. We generated mAbs specific for the equine C-C motif chemokine ligands (CCL) CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES) and CCL11 (eotaxin) using hybridoma technology. Antibody specificity was confirmed by intracellular staining of Chinese Hamster Ovary cells transfected with expression vectors encoding for CCL2, CCL3, CCL5, or CCL11...
October 2018: Veterinary Immunology and Immunopathology
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