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B cell memory

Stefanie Kuerten, Leila J Jackson, Joel Kaye, Timothy L Vollmer
Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells...
October 12, 2018: CNS Drugs
Aliyah M Weinstein, Nicolas A Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, Frédérique Peschaud, Jean-François Emile, Laetitia Marisa, Wolf H Fridman, Walter J Storkus, Catherine Sautès-Fridman
IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
Stefan Nagel, Roderick A F MacLeod, Corinna Meyer, Maren Kaufmann, Hans G Drexler
Homeobox genes encode transcription factors which regulate basic processes in development and cell differentiation. Several members of the NKL subclass are deregulated in T-cell progenitors and support leukemogenesis. We have recently described particular expression patterns of nine NKL homeobox genes in early hematopoiesis and T-cell development. Here, we screened NKL homeobox gene activities in normal B-cell development and extended the NKL-code to include this lymphoid lineage. Analysis of public expression profiling datasets revealed that HHEX and NKX6-3 were the only members differentially active in naïve B-cells, germinal center B-cells, plasma cells and memory B-cells...
2018: PloS One
Alissa K Rutman, Sarita Negi, Marco Gasparrini, Craig P Hasilo, Jean Tchervenkov, Steven Paraskevas
The autoimmune response which characterizes Type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EV) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EV isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation. We show that human islet EV are internalized by monocytes and B cells and lead to an increase in T-helper 1, 2 and 17 cytokine expression, as well as T and B cell proliferation...
October 10, 2018: Endocrinology
Amelia N Chang, Zhuoyi Liang, Hai-Qiang Dai, Aimee M Chapdelaine-Williams, Nick Andrews, Roderick T Bronson, Bjoern Schwer, Frederick W Alt
Genetically modified mice are commonly generated by the microinjection of pluripotent embryonic stem (ES) cells into wild-type host blastocysts1 , producing chimeric progeny that require breeding for germline transmission and homozygosity of modified alleles. As an alternative approach and to facilitate studies of the immune system, we previously developed RAG2-deficient blastocyst complementation2 . Because RAG2-deficient mice cannot undergo V(D)J recombination, they do not develop B or T lineage cells beyond the progenitor stage2 : injecting RAG2-sufficient donor ES cells into RAG2-deficient blastocysts generates somatic chimaeras in which all mature lymphocytes derive from donor ES cells...
October 10, 2018: Nature
Timothy N Hoang, Justin L Harper, Maria C Pino, Hong Wang, Luca Micci, Colin T King, Colleen S McGary, Julia B McBrien, Barbara Cervasi, Guido Silvestri, Mirko Paiardini
The bone marrow (BM) is the key anatomic site for hematopoiesis and plays a significant role in the homeostasis of mature T cells. However, very little is known on the phenotype of BM-derived CD4+ T cells, their fate during SIV infection, and their contribution to viral persistence during antiretroviral therapy (ART). Here, we characterized the immunologic and virologic status of BM-derived CD4+ T cells in rhesus macaques prior to SIV infection, during the early chronic phase of infection, and after ART. We found that BM memory CD4+ T cells are significantly depleted following SIV infection, at levels that are similar to those measured in PB...
October 10, 2018: Journal of Virology
Elizabeth N da Silva, Alan Baker, Jalila Alshekaili, Krishna Karpe, Matthew C Cook
BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. METHODS: We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule...
2018: PloS One
Suparna Dutt, Michelle B Atallah, Yoshitaka Minamida, Alexander Filatenkov, Kent P Jensen, Bettina P Iliopoulou, Rasa Tamosiuniene, Jeffrey Waters, Edgar G Engleman, Samuel Strober
Conventional local tumor irradiation (LTI), delivered in small daily doses over several weeks, is used clinically as a palliative, rather than curative, treatment for chemotherapy-resistant diffuse large B-cell lymphoma (DLBCL) for patients who are ineligible for hematopoietic cell transplantation. Our goal was to test the hypothesis that accelerated, but not conventional, LTI would be more curative by inducing T cell-mediated durable remissions. We irradiated subcutaneous A20 and BL3750 lymphoma tumors in mice with a clinically relevant total radiation dose of 30 Gy LTI, delivered in 10 doses of 3 Gy over 4 days (accelerated irradiation) or as 10 doses of 3 Gy over 12 days (conventional irradiation)...
October 9, 2018: Blood Advances
Natalia Gawron, M Choiński, B Szymańska-Kotwica, A Pluta, M Sobańska, A R Egbert, A Desowska, T Wolak, A Horban, E Firląg-Burkacka, P Bieńkowski, H Sienkiewicz-Jarosz, A Scińska-Bieńkowska, B Biswal, S M Rao, R Bornstein, E Łojek
It is yet unclear if people infected with human immunodeficiency virus (HIV+) on stable, combined antiretroviral therapies (cARTs) decline with age at the same or greater rate than healthy people. In this study, we examined independent and interactive effects of HIV, age, and HIV-related clinical parameters on neuropsychological functioning and brain regional volume in a sizable group of Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell count, CD4 cell count during participation in the study, duration of HIV infection, or duration of cART along with age...
October 8, 2018: Journal of Neurovirology
Leonid Yurkovetskiy, Mehmet Hakan Guney, Kyusik Kim, Shih Lin Goh, Sean McCauley, Ann Dauphin, William E Diehl, Jeremy Luban
Host factors that silence provirus transcription in CD4+ memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs1 . These same factors, however, must be overcome for HIV-1 to propagate. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus transcription. Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3 ubiquitin ligase that degrade SAMHD1 and increase reverse transcription2-4 . Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not explained by SAMHD1 degradation5-8 ...
October 8, 2018: Nature Microbiology
Jonathan E Schoenhals, Taylor R Cushman, Hampartsoum B Barsoumian, Ailin Li, Alexandra P Cadena, Sharareh Niknam, Ahmed I Younes, Mauricio da Silva Caetano, Maria Angelica Cortez, James W Welsh
Despite the potential to cure metastatic disease, immunotherapy on its own often fails outright or early on due to tumor immune evasion. To address this obstacle, we investigated combinations of anti-GITR, anti-PD1 and radiation therapy (XRT) in our previously developed anti-PD1 resistant 344SQ non-small cell lung adenocarcinoma preclinical tumor model. We hypothesized that targeting multiple mechanisms of immune evasion with this triple therapy would lead to an enhanced tumor-specific immune response and improve survival more so than any mono- or dual therapy...
2018: Frontiers in Immunology
Rebeca Singh Sidhu-Muñoz, Pilar Sancho, Axel Cloeckaert, Michel Stanislas Zygmunt, María Jesús de Miguel, Carmen Tejedor, Nieves Vizcaíno
Brucella ovis is a non-zoonotic Brucella species lacking specific vaccine. It presents a narrow host range, a unique biology relative to other Brucella species, and important distinct surface properties. To increase our knowledge on its peculiar surface and virulence features, and seeking to develop a specific vaccine, multiple mutants for nine relevant cell-envelope-related genes were investigated. Mutants lacking Omp10 plus Omp19 could not be obtained, suggesting that at least one of these lipoproteins is required for viability...
2018: Frontiers in Microbiology
Danielle I Stanisic, James Fink, Johanna Mayer, Sarah Coghill, Letitia Gore, Xue Q Liu, Ibrahim El-Deeb, Ingrid B Rodriguez, Jessica Powell, Nicole M Willemsen, Sai Lata De, Mei-Fong Ho, Stephen L Hoffman, John Gerrard, Michael F Good
BACKGROUND: The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria...
October 8, 2018: BMC Medicine
Amine Meliani, Florence Boisgerault, Romain Hardet, Solenne Marmier, Fanny Collaud, Giuseppe Ronzitti, Christian Leborgne, Helena Costa Verdera, Marcelo Simon Sola, Severine Charles, Alban Vignaud, Laetitia van Wittenberghe, Giorgia Manni, Olivier Christophe, Francesca Fallarino, Christopher Roy, Alicia Michaud, Petr Ilyinskii, Takashi Kei Kishimoto, Federico Mingozzi
Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates...
October 5, 2018: Nature Communications
James P Phipps, Karen M Haas
Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines...
October 4, 2018: Journal of Infectious Diseases
Charlotte M Mousset, Willemijn Hobo, Yun Ji, Hanny Fredrix, Valeria De Giorgi, Robert D Allison, Michel G D Kester, J H Frederik Falkenburg, Nicolaas P M Schaap, Joop H Jansen, Luca Gattinoni, Harry Dolstra, Anniek B van der Waart
Adoptive T cell therapy has shown clinical potential for patients with cancer, though effective treatment is dependent on longevity and potency of the exploited tumor-reactive T cells. Previously, we showed that ex vivo inhibition of AKT using the research compound Akt-inhibitor VIII retained differentiation and improved functionality of minor histocompatibility antigen (MiHA)-specific CD8+ T cells. Here, we compared a panel of clinically applicable AKT-inhibitors with an allosteric or adenosine triphosphate-competitive mode of action...
2018: Oncoimmunology
Marco Lanzillotta, Emanuel Della-Torre, Raffaella Milani, Enrica Bozzolo, Emanuele Bozzalla-Cassione, Lucrezia Rovati, Paolo Giorgio Arcidiacono, Stefano Partelli, Massimo Falconi, Fabio Ciceri, Lorenzo Dagna
BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. METHODS: Thirty patients were treated with glucocorticoids according to international guidelines...
October 3, 2018: Arthritis Research & Therapy
Raja Sekhar Sanna, Subramanyam Muthangi, Chandrasekhar Sagar B K, Sambe Asha Devi
It is frequently accepted that grape seed proanthocyanidins (GSPs) are efficient antioxidants and beneficial in improving cognitive functions. However, diabetes (T1DM)-associated declines in learning and memory and the possibilities of GSPs in overcoming this loss needs to be examined. The present study was designed to examine the correlation, if one exists, between cognitive behavior and neuronal survival in the prefrontal cortex (PFC) in streptozotocin (STZ)-induced diabetic Wistar rats as well as to further clarify whether the correlation exists...
October 3, 2018: Metabolic Brain Disease
Amanda B Macedo, Camille L Novis, Caroline M De Assis, Eric S Sorensen, Paula Moszczynski, Szu-Han Huang, Yanqin Ren, Adam M Spivak, R Brad Jones, Vicente Planelles, Alberto Bosque
The presence of a reservoir of latently infected cells in HIV-infected patients is a major barrier towards finding a cure. One active cure strategy is to find latency-reversing agents that induce viral reactivation, thus leading to immune cell recognition and elimination of latently infected cells, known as the shock-and-kill strategy. Therefore, the identification of molecules that reactivate latent HIV and increase immune activation has the potential to further these strategies into the clinic. Here, we characterized synthetic molecules composed of a TLR2 and a TLR7 agonist (dual TLR2/7 agonists) as latency-reversing agents and compared their activity with that of the TLR2 agonist Pam2CSK4 and the TLR7 agonist GS-9620...
October 4, 2018: JCI Insight
Arshpreet Kaur, Deepika Kannan, Surinder K Mehta, Shailja Singh, Deepak B Salunke
Currently there is no efficient vaccine available against clinical malaria. However, continuous efforts have been committed to develop powerful antimalarial vaccine by discovery of novel antigens with in-depth understanding of its nature, immunogenicity and presentation (delivery adjuvants). Moreover, another important part of vaccine development includes discovery of better immunostimulatory formulation components (immunostimulants). A protective vaccine against malaria requires antigen-specific B and T helper cell responses as well as CTL responses...
October 3, 2018: Expert Opinion on Therapeutic Patents
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