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https://www.readbyqxmd.com/read/28938005/recombinant-vaccines-of-a-cd4-t-cell-epitope-promote-efficient-control-of-paracoccidioides-brasiliensis-burden-by-restraining-primary-organ-infection
#1
Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay...
September 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#2
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28935575/non-pathological-infection-of-macaques-by-an-attenuated-mycobacterial-vaccine-is-not-reactivated-in-the-setting-of-hiv-coinfection
#3
Taylor Wayne Foreman, Ashley Victoria Veatch, Denae Nadine LoBato, Peter John Didier, Lara Angela Doyle-Meyers, Kasi Elizabeth Russell-Lodrigue, Andrew Alan Lackner, Konstantin Gus Kousoulas, Shabaana Abdul Khader, Deepak Kaushal, Smriti Mehra
Failure to replace BCG with efficacious anti-TB vaccines have prompted out-of-the-box thinking, including pulmonary vaccination in order to elicit local immunity. MtbΔsigH, a stress-response attenuated strain, protected against lethal TB when used to vaccinate macaques via inhalation. While live mycobacterial vaccines show promising efficacy, HIV co-infection and the resulting immunodeficiency prompts safety concerns about their use. We assessed the persistence and safety of MtbΔsigH, delivered directly to the lungs, in the setting of HIV coinfection...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#4
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#5
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934393/neurofibromatosis-type-1-alternative-splicing-is-a-key-regulator-of-ras-erk-signaling-and-learning-behaviors-in-mice
#6
Hieu T Nguyen, Melissa N Hinman, Xuan Guo, Alok Sharma, Hiroyuki Arakawa, Guangbin Luo, Hua Lou
Appropriate activation of the Ras/extracellular signal-regulated kinase (ERK) protein signaling cascade within the brain is crucial for optimal learning and memory. One key regulator of this cascade is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by converting active Ras is bound to guanosine triphosphate, activating Ras into inactive Ras is bound to guanosine diphosphate, inactivating Ras. A previous study using embryonic stem cells and embryonic stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alternative splicing of Nf1 exon 23a...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934217/elevated-humoral-response-to-cytomegalovirus-in-hiv-infected-individuals-with-poor-cd4-t-cell-immune-recovery
#7
Elisabet Gómez-Mora, Marta Massanella, Elisabet García, David Giles, Marta Bernadó, Victor Urrea, Jorge Carrillo, Dan Ouchi, Jordi Puig, Eugenia Negredo, Bonaventura Clotet, Julià Blanco, Cecilia Cabrera
Some HIV-infected c-ART-suppressed individuals show incomplete CD4+ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4+ T-cell counts >350 cells/μL (immunoconcordant, n = 133) or <350 cells/μL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery...
2017: PloS One
https://www.readbyqxmd.com/read/28933579/innate-immune-cells-for-immunotherapy-of-autoimmune-and-cancer-disorders
#8
Carolina Schäfer, Gabriel Ascui, Carolina H Ribeiro, Mercedes López, Rafael Prados-Rosales, Pablo A González, Susan M Bueno, Claudia A Riedel, Andrés Baena, Alexis M Kalergis, Leandro J Carreño
Modulation of the immune system has been widely targeted for the treatment of several immune-related diseases, such as autoimmune disorders and cancer, due to its crucial role in these pathologies. Current available therapies focus mainly on symptomatic treatment and are often associated with undesirable secondary effects. For several years, remission of disease and subsequently recovery of immune homeostasis has been a major goal for immunotherapy. Most current immunotherapeutic strategies are aimed to inhibit or potentiate directly the adaptive immune response by modulating antibody production and B cell memory, as well as the effector potential and memory of T cells...
September 21, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#9
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#10
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931830/circulating-mycobacterium-tuberculosis-dosr-latency-antigen-specific-polyfunctional-regulatory-il10-th17-cd4-t-cells-differentiate-latent-from-active-tuberculosis
#11
Srabanti Rakshit, Vasista Adiga, Soumya Nayak, Pravat Nalini Sahoo, Prabhat Kumar Sharma, Krista E van Meijgaarden, Anto Jesuraj Uk J, Chirag Dhar, George D Souza, Greg Finak, Stephen C De Rosa, Tom H M Ottenhoff, Annapurna Vyakarnam
The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931676/protective-humoral-immunity-in-the-cns-requires-peripheral-cd19-dependent-germinal-center-formation-following-coronavirus-encephalomyelitis
#12
Jeffrey R Atkinson, Cornelia C Bergmann
B cell subsets with phenotypes characteristic of naïve, non-isotype-switched, memory (Bmem), and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection infiltration of protective ASC occurs after T cell mediated viral control, and is preceded by accumulation of non-isotype switched IgD(+) and IgM(+) B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) in driving humoral immune responses in the infected CNS is poorly defined...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931520/dna-priming-increases-frequency-of-t-cell-responses-to-a-vsv-hiv-vaccine-with-specific-enhancement-of-cd8-t-cell-responses-by-il-12-pdna
#13
Shuying S Li, Nidhi K Kochar, Marnie Elizaga, Christine M Hay, Gregory J Wilson, Kristen W Cohen, Stephen C De Rosa, Rong Xu, Ayuko Ota-Setlik, Daryl Morris, Greg Finak, Mary Allen, Hong-Van Tieu, Ian Frank, Magdalena E Sobieszczyk, Drew Hannaman, Raphael Gottardo, Peter B Gilbert, Georgia D Tomaras, Lawrence Corey, David K Clarke, Michael A Egan, John H Eldridge, M Juliana McElrath, Nicole Frahm
HVTN 087 assessed the effect of increasing doses of pIL-12 adjuvant on the immunogenicity of a HIV-1 multi-antigen (MAG) DNA vaccine delivered by electroporation and boosted with an attenuated VSV-Gag vaccine. We randomized 100 healthy adults to receive placebo, or 3mg HIV-MAG (gag/pol, env, nef/tat/vif) DNA vaccine co-administered with pIL-12 at 0μg, 250μg, 1,000μg or 1,500μg intramuscularly by electroporation at 0, 1 and 3 months followed by intramuscular inoculation with 3.4×10(7) PFU VSV-Gag vaccine at 6 months...
September 20, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28930701/leukocyte-telomere-length-t-cell-composition-and-dna-methylation-age
#14
Brian H Chen, Cara L Carty, Masayuki Kimura, Jeremy D Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P Reiner, Abraham Aviv
Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826)...
September 20, 2017: Aging
https://www.readbyqxmd.com/read/28930685/human-tissue-resident-memory-t-cells-are-defined-by-core-transcriptional-and-functional-signatures-in-lymphoid-and-mucosal-sites
#15
Brahma V Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L Friedman, Yufeng Shen, Donna L Farber
Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930287/exposure-to-human-alveolar-lining-fluid-enhances-mycobacterium-bovis-bcg-vaccine-efficacy-against-mycobacterium-tuberculosis-infection-in-a-cd8-t-cell-dependent-manner
#16
J I Moliva, A P Hossfeld, C H Canan, V Dwivedi, M D Wewers, G Beamer, J Turner, J B Torrelles
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930286/molecular-and-cellular-signatures-underlying-superior-immunity-against-bordetella-pertussis-upon-pulmonary-vaccination
#17
R Hm Raeven, J Brummelman, J LA Pennings, L van der Maas, K Helm, W Tilstra, A van der Ark, A Sloots, P van der Ley, W van Eden, W Jiskoot, E van Riet, C Acm van Els, G Fa Kersten, W Gh Han, B Metz
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28929596/hypogammaglobulinemia-in-children-a-warning-sign-to-look-deeply
#18
Karina Mescouto de Melo, Maria Isabel de Moraes-Pinto, Luís E C Andrade, Reinaldo Salomão, Milena K C Brunialti, Vanessa S Ferreira, Beatriz T Costa-Carvalho
This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as B-cell subsets in non-consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T-cell and B-cell subpopulations. T-cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid...
October 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28928269/perturbed-cd8-t-cell-immunity-across-universal-influenza-epitopes-in-the-elderly
#19
Thi H O Nguyen, Sneha Sant, Nicola L Bird, Emma J Grant, E Bridie Clemens, Marios Koutsakos, Sophie A Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska
Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8(+) T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8(+) T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8(+) T cells...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28927891/vitiligo-skin-is-imprinted-with-resident-memory-cd8-t-cells-expressing-cxcr3
#20
Katia Boniface, Clément Jacquemin, Anne-Sophie Darrigade, Benoît Dessarthe, Christina Martins, Nesrine Boukhedouni, Charlotte Vernisse, Alexis Grasseau, Denis Thiolat, Jérôme Rambert, Fabienne Lucchese, Antoine Bertolotti, Khaled Ezzedine, Alain Taieb, Julien Seneschal
Vitiligo is a chronic auto-immune depigmenting skin disorder that results from a loss of melanocytes. Multiple combinatorial factors have been involved in disease development, with a prominent role of the immune system, in particular T cells. After repigmentation, vitiligo frequently recurs in the same area, suggesting that vitiligo could involve the presence of resident memory T cells (TRM). We sought to perform a thorough characterization of the phenotype and function of skin memory T cells in vitiligo. We show that stable and active vitiligo perilesional skin is enriched with a population of CD8 TRM expressing both CD69 and CD103 compared to psoriasis and control unaffected skin...
September 16, 2017: Journal of Investigative Dermatology
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