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Susan Pereira Ribeiro; Vania Gomes De Moura Mattaraia; Rafael Ribeiro Almeida; Elizabeth Juliana Ghiuro Valentine; Natiely Silva Sales; Luís Carlos S. Ferreira; Luiz Carlos Sa-Rocha; Lucas Cauê Jacintho; Vinicius Canato Santana; John Sidney; Alessandro Sette; Daniela Santoro Rosa; Jorge Kalil; Edecio Cunha-Neto
... Over the last few decades, several emerging or reemerging viral diseases with no readily available vaccines have ravaged the world. A platform to fastly generate vaccines inducing potent and durable neutralizing antibody and T cell responses is sorely needed. Bioinformatically identified epitope-based vaccines can focus on immunodominant T cell epitopes and induce more potent immune responses than ...
... PURPOSE: Particular interest is now given to the potential of dietary supplements as alternative non-pharmacological approaches in intestinal inflammation handling. In this aim, this study evaluates the efficiency of fish collagen peptides, Naticol®Gut, on colonic inflammation. METHODS: Wild type and Mannose receptor-deficient in the myeloid lineage C57BL/6 mice were administered with Dextran Sodi ...
Jessica A. Flynn; Teresa Weber; Pedro J. Cejas; Kara S. Cox; Sinoeun Touch; Lauren A. Austin; Yangsi Ou; Michael P. Citron; Bin Luo; Marian E. Gindy; Kapil Bahl; Giuseppe Ciaramella; Amy S. Espeseth; Lan Zhang
... In response to immune pressure, influenza viruses evolve, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response capable of recognizing multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the efficacy and immunogenicity of mRNA vaccines encoding either the conserve ...
Vianney Tricou; Raphael Gottardo; Michael A. Egan; Frédéric Clement; Geert Leroux-Roels; Xavier Sáez-Llorens; Astrid Borkowski; Derek Wallace; Hansi J. Dean
CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; cell-mediated immunity; cross reaction; dengue; flow cytometry; interleukin-2; live vaccines; serotypes; Panama
Abstract:
... As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical tr ...
... Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a D ...
David C. Soler; Amber Kerstetter-Fogle; Andrew B. Young; Pat Rayman; James H. Finke; Sarah M. Debanne; Kevin D. Cooper; Jill Barnholtz-Sloan; Andrew E. Sloan; Thomas S. McCormick
... Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14⁺ HLA-DRⁿᵉᵍ/ˡᵒʷ) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14⁺ HLA-DRʰⁱᵍʰ monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarke ...
... Infants’ universal hepatitis A virus (HAV) single-dose vaccination has been highly effective for controlling HAV infection in Argentina, and in other Latin-American countries that adopted that strategy. Although antibodies wane over time, this has not been associated with HAV outbreaks or breakthrough infections, suggesting a relevant role for memory immunity. This study assessed long term humoral ...
... Chronic obstructive pulmonary disease (COPD) is a disabling/fatal disease characterized by progressive pulmonary function decline, and there are currently few drugs that can effectively reverse the decline in lung function; therefore, it is necessary to find novel drug targets. CD8⁺ T cells might be a new therapeutic target for alleviating lung tissue destruction and improving pulmonary function i ...
Jonas Lötscher; Adrià-Arnau Martí i Líndez; Nicole Kirchhammer; Elisabetta Cribioli; Greta Maria Paola Giordano Attianese; Marcel P. Trefny; Markus Lenz; Sacha I. Rothschild; Paolo Strati; Marco Künzli; Claudia Lotter; Susanne H. Schenk; Philippe Dehio; Jordan Löliger; Ludivine Litzler; David Schreiner; Victoria Koch; Nicolas Page; Dahye Lee; Jasmin Grählert; Dmitry Kuzmin; Anne-Valérie Burgener; Doron Merkler; Miklos Pless; Maria L. Balmer; Walter Reith; Jörg Huwyler; Melita Irving; Carolyn G. King; Alfred Zippelius; Christoph Hess
... The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8⁺ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-suff ...
... Sialic acids are negatively charged carbohydrates that cap the glycans of glycoproteins and glycolipids. Sialic acids are involved in various biological processes including cell–cell adhesion and immune recognition. In dendritic cells (DCs), the major antigen-presenting cells of the immune system, sialic acids emerge as important regulators of maturation and interaction with other lymphocytes incl ...
... In the late 1980s and early 1990s, the hunt for a transporter molecule ostensibly responsible for the translocation of peptides across the endoplasmic reticulum (ER) membrane yielded the successful discovery of transporter associated with antigen processing (TAP) protein. TAP is a heterodimer complex comprised of TAP1 and TAP2, which utilizes ATP to transport cytosolic peptides into the ER across ...
... Tumor infiltrating lymphocytes (TILs) are cells that are present inside the tumor environment, of which include T cells, B cells and natural killer (NK) cells. At present, TILs are used for immunotherapy in various cancers. Knowledge on adoptive transfer of TILs in ovarian cancer is still limited, especially regarding TIL expansion methods. Therefore, the aim of our study was to compare the qualit ...
... A major clinical challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) is identifying those that may benefit from adjuvant chemotherapy versus those that will not. Thus, there is a need for a robust and convenient biomarker for predicting chemotherapy response in PDAC patients. In this study, network inference was conducted by integrating the differentially expressed cell cy ...
... Traditional pathological diagnoses and clinical methods are insufficient to accurately predict the prognosis of lung adenocarcinoma (LUAD). Epithelial-mesenchymal transition (EMT) process is closely related to tumor cell migration. However, the prognostic value of EMT-related genes in LUAD is still unclear. In this study, we collected bulk RNA-sequencing (RNA-seq) and microarray data of LUAD patie ...
... Epitope peptides are not suitable for nasal administration immunity due to their poor immunogenicity and low delivery efficiency. Here, we reported an intranasal self-assembled nanovaccine (I-OVA NE), which was loaded with the peptides IKVAV-OVA₂₅₇–₂₆₄ (I-OVA), a laminin peptide (Ile-Lys-Val-ala-Val, IKVAV) and OVA₂₅₇–₂₆₄ epitope conjugated peptide. This nanovaccine with I-OVA at a concentration o ...
CD8-positive T-lymphocytes; HLA antigens; Hepatitis B virus; Hepatitis C virus; Hepatitis delta virus; Human immunodeficiency virus; adaptive immunity; humans; interferons; liver cirrhosis; mixed infection; pathogenesis; satellite viruses; vertebrate viruses
Abstract:
... The hepatitis delta virus (HDV) is the smallest known human virus, yet it causes great harm to patients co-infected with hepatitis B virus (HBV). As a satellite virus of HBV, HDV requires the surface antigen of HBV (HBsAg) for sufficient viral packaging and spread. The special circumstance of co-infection, albeit only one partner depends on the other, raises many virological, immunological, and pa ...
Megan L. Burger; Amanda M. Cruz; Grace E. Crossland; Giorgio Gaglia; Cecily C. Ritch; Sarah E. Blatt; Arjun Bhutkar; David Canner; Tamina Kienka; Sara Z. Tavana; Alexia L. Barandiaran; Andrea Garmilla; Jason M. Schenkel; Michelle Hillman; Izumi de los Rios Kobara; Amy Li; Alex M. Jaeger; William L. Hwang; Peter M.K. Westcott; Michael P. Manos; Marta M. Holovatska; F. Stephen Hodi; Aviv Regev; Sandro Santagata; Tyler Jacks
... CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdom ...
CD8-positive T-lymphocytes; breast neoplasms; epitopes; humans; immune response; lungs; metastasis; mice; mutants; peptides; prognosis; signal peptide; tandem repeat sequences; vaccination; vaccine development; vaccines
Abstract:
... The identification of novel targets for cancer immunotherapy and the development of new vaccine immunogens are subjects of permanent interest. MUC1 is an overexpressed antigen found in most tumors, and its overexpression correlates with poor prognosis. Many attempts to direct the immune response against MUC1 in tumor cells have failed, including several clinical trials. We have previously develope ...
... B lymphocytes have well-established effector roles during viral infections, including production of antibodies and functioning as antigen-presenting cells for CD4+ and CD8+ T cells. B cells have also been shown to regulate immune responses and induce regulatory T cells (Tregs). In the Friend virus (FV) model, Tregs are known to inhibit effector CD8+ T-cell responses and contribute to virus persist ...
... Infection with Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), remains a significant global epidemic. Host resistance to Mtb depends on both adaptive and innate immunity mechanisms, including development of antigen-specific CD4 and CD8 T cells, production of inflammatory cytokines, bacterial phagocytosis and destruction within phagolysosomes, host cell apoptosis, and ...
Mayte Medrano; Ana Lemus-Conejo; Sergio Lopez; Maria C. Millan-Linares; Maria A. Rosillo; Manuel Muñiz; Rocio Calderon; Sara Jaramillo; Jose A. Perez-Simon; Francisco J.G. Muriana; Rocio Abia
... Obesity is associated with disruptions in the adaptive immune system; however, dietary fatty acids in high-fat diets (HFDs) that induce obesity have consequences that are currently unclear regarding T-cell maintenance in bone marrow (BM). C57BL/6J mice were randomly assigned to isocaloric HFDs formulated with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), o ...
... We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. R ...
... Interfering with signalling pathways by targeting cell surface proteins has become an important strategy in the development of novel therapeutic agents. Notably, interfering with cytokine signalling revolutionised the treatment of chronic diseases. Cytokines can induce a range of effects that are not always accounted for in assays detecting cytokine binding to cell surface receptors and/or proxima ...
... Zika virus (ZIKV) caused over two million human infections in more than 80 countries around 2015–2016. Current vaccines under development are mostly focused on inducing antibodies that despite capable of inhibiting the virus, may have the potential to trigger antibody dependent enhancement (ADE). T cell vaccines that do not induce antibodies targeting viral surface will unlikely cause ADE, but be ...
... HIV elite controllers (ECs) are characterized by the spontaneous control of viral replication, and by metabolic and autophagic profiles which favor anti-HIV CD4 and CD8 T-cell responses. Extracellular acyl coenzyme A binding protein (ACBP) acts as a feedback inhibitor of autophagy. Herein, we assessed the circulating ACBP levels in ECs, compared to people living with HIV (PLWH) receiving antiretro ...
Abelmoschus esculentus; CD8-positive T-lymphocytes; body weight; carcinogenicity; diethylnitrosamine; doxorubicin; immunomodulation; interleukin-2; liver; macrophages; males; okra; polysaccharides; Indonesia
Abstract:
... Polysaccharides have long been recognized as the anticancer agent with low toxicity and slight side effects. Okra (Abelmoschus esculentus L.), a flowering plant from the Malvaceae family that is found in tropical, subtropical, and warm temperate regions around the world. Hence, no in vivo studies have addressed the anticancer and immunomodulatory potential of polysaccharides from okra pods grown i ...
Feliciana Real-Fernández; Alessandra Gallo; Francesca Nuti; Lorenzo Altamore; Gloria Giovanna Del Vescovo; Pietro Traldi; Eugenio Ragazzi; Paolo Rovero; Annunziata Lapolla; Anna Maria Papini
... Diagnosis of Latent Autoimmune Diabetes in Adults (LADA) is based on the adult-age, anti-islet autoantibodies, and temporary insulin-independence. As in Type-1-Diabetes (T1DM), autoimmunity may trigger LADA and enteroviruses-infections can play a role. Anti-human Glutamic-Acid-Decarboxylase (hGAD) autoantibodies are accepted clinical biomarkers, but do not discriminate LADA vs. T1DM. The hypothesi ...
... T‐bet and Eomes are two related transcription factors (TFs) that regulate the differentiation of cytotoxic lymphocytes such as Natural Killer (NK) cells and CD8 T cells. Recent genome‐wide analyses suggest they have complementary roles in instructing the transcriptional program of NK cells, although their DNA binding sites appear to be very similar. In this essay, we discuss the mechanisms that co ...
... Id3, an inhibitor of DNA binding protein, plays important roles in the function and homeostasis of effector and memory T cells. Recent evidence has shown that Id3 is also implicated in CD8 T cell exhaustion. However, whether and how Id3 might regulate effector function or exhaustion of CD8 T cells, especially in the tumor setting, is still unknown. Here, we first showed that Id3 expression was imp ...
Katlyn Lederer; Emily Bettini; Kalpana Parvathaneni; Mark M. Painter; Divyansh Agarwal; Kendall A. Lundgreen; Madison Weirick; Kavitha Muralidharan; Diana Castaño; Rishi R. Goel; Xiaoming Xu; Elizabeth M. Drapeau; Sigrid Gouma; Jordan T. Ort; Moses Awofolaju; Allison R. Greenplate; Carole Le Coz; Neil Romberg; Jennifer Trofe-Clark; Gregory Malat; Lisa Jones; Mark Rosen; Daniela Weiskopf; Alessandro Sette; Behdad Besharatian; Mary Kaminiski; Scott E. Hensley; Paul Bates; E. John Wherry; Ali Naji; Vijay Bhoj; Michela Locci
... Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle ...
CD8-positive T-lymphocytes; HIV infections; Simian immunodeficiency virus; disease progression; early selection; epitopes; haplotypes; immunosuppression; major histocompatibility complex; models; mutation; research; virus replication
Abstract:
... CD8⁺ T-cell responses exert strong suppressive pressure on viral replication and select for viral escape mutations in HIV infection. Multiple viral epitopes restricted by major histocompatibility complex class I (MHC-I) are targeted by CD8⁺ T cells. Sequential selection of viral escape mutations in individual epitope-coding regions could result in failure in CD8⁺ T cell-based viral control leading ...
... Background: Sialoadhesin (CD169) has been found to be overexpressed in the blood of COVID-19 patients and identified as a biomarker in early disease. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. Methods: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD16 ...
... Cross-reactive T cell immunity to seasonal coronaviruses (HCoVs) may lead to immunopathology or protection during SARS-CoV2 infection. To understand the influence of cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8⁺ T cell epitopes, restricted through HLA-A and B alleles. Conservation analysis was carried out for these epito ...
... The novel virus “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” has been responsible for the worldwide pandemic causing huge devastation and deaths since December 2019. The disease caused by this virus is known as COVID-19. The present study is based on immuno-informatics approach to develop a multi-epitope-loaded peptide vaccine to combat the COVID-19 menace. Here, we have reported ...
... Influenza virus is one of the most rapidly evolving human pathogens and causes significant morbidity and mortality worldwide. This feature enables the virus to avoid natural or vaccine-induced immunity. For this reason, there is an intensive search for new approaches to create a universal influenza vaccine. Here, we propose pipelines based on modern prediction algorithms that allowed us to select ...
... Plasmodium falciparum (P. falciparum) is a leading causative agent of malaria, an infectious disease that can be fatal. Unfortunately, control measures are becoming less effective over time. A vaccine is needed to effectively control malaria and lead towards the total elimination of the disease. There have been multiple attempts to develop a vaccine, but to date, none have been certified as approp ...
... At the beginning of the year 2020, the world was struck with a global pandemic virus referred to as SARS-CoV-2 (COVID-19) which has left hundreds of thousands of people dead. To control this virus, vaccine design becomes imperative. In this study, potential epitopes-based vaccine candidates were explored. Six hundred (600) genomes of SARS-CoV-2 were retrieved from the viPR database to generate CD8 ...
... Human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. Vaccination has been an approach successfully used as a prophylactic measure against this infectious agent in patients without previous contact with the genotypes present in the vaccine. In this work, we use a computational approach to predict CD8 T cell epitopes from HPV proteins to promote c ...
... Vaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular responses after vaccination with a two-dose schedule in a Crohn’s disease patient t ...
CD8-positive T-lymphocytes; COVID-19 infection; Severe acute respiratory syndrome coronavirus 2; antibodies; computer simulation; epitopes; evolution; immune response; infection; mutants; nucleocapsid; peptides; viral load; Brazil; South Africa
Abstract:
... SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, little attention has been given to pre-existing and induced SARS-CoV-2-spe ...
... Angiopoietin-like 4 (ANGPTL4) is involved in inflammation-associated diseases, such as rheumatoid arthritis, type 2 diabetes, atherosclerosis, and chronic obstructive pulmonary disease. The role of ANGPTL4 in the pathogenesis of inflammatory bowel disease (IBD) remains unknown. Here, the plasma ANGPTL4 levels peaked on days 3 and 5, and expression of ANGPTL4 of inflamed colons peaked on days 5 and ...
... Accumulating clinical data shows that less than half of patients are beneficial from PD-1/PD-L1 blockage therapy owing to the limited infiltration of effector immune cells into the tumor and abundant of the immunosuppressive factors in the tumor microenvironment. In this study, PD-L1 inhibition therapy and BRAF-targeted therapy, which showed clinical benefit, were combined in a CXCR4-targeted nano ...
... This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activated in the presence of MAF- and DF-conditioned med ...
... Cytomegaloviruses (CMVs) are controlled by innate and adaptive immune responses in an immunocompetent host while causing multiple organ diseases in an immunocompromised host. A risk group of high clinical relevance comprises transiently immunocompromised recipients of hematopoietic cell transplantation (HCT) in the “window of risk” between eradicative therapy of hematopoietic malignancies and comp ...
Ye Feng; Haiping Jiang; Min Qiu; Liang Liu; Shengmei Zou; Yun Li; Qianpeng Guo; Ning Han; Yingqiang Sun; Kui Wang; Lantian Lu; Xinlei Zhuang; Shanshan Zhang; Shuqing Chen; Fan Mo
... Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high ...
Can Cui; Jiawei Wang; Eric Fagerberg; Ping-Min Chen; Kelli A. Connolly; Martina Damo; Julie F. Cheung; Tianyang Mao; Adnan S. Askari; Shuting Chen; Brittany Fitzgerald; Gena G. Foster; Stephanie C. Eisenbarth; Hongyu Zhao; Joseph Craft; Nikhil S. Joshi
... CD4 T follicular helper (TFH) cells support B cells, which are critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found enrichment of TFH cell transcriptional signature correlates with GC B cell signature and with prolonged survival in individuals with lung adenocarcinoma (LUAD). We further developed a murine LUAD model in which tumo ...
... Antiretroviral therapy (ART) controls human immunodeficiency virus 1 (HIV-1) replication and prevents disease progression but does not eradicate HIV-1. The persistence of a reservoir of latently infected cells represents the main barrier to a cure. “Shock and kill” is a promising strategy involving latency reversing agents (LRAs) to reactivate HIV-1 from latently infected cells, thus exposing the ...
CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; adults; antiretroviral agents; blood glucose; blood pressure; body fat; body mass index; bone density; cholesterol; clinical examination; dual-energy X-ray absorptiometry; high density lipoprotein; hypercholesterolemia; inflammation; interleukin-6; low density lipoprotein; morbidity; muscle tissues; necrosis; neoplasms; nutrition; obesity; triacylglycerols
Abstract:
... Objectives: Normal weight obesity (NWO) is defined as a condition of normal body weight, but with high body fat percentage. Clinical and immunologic implications of NWO in persons living with HIV (PLHIV) remain unknown. The aim of this study was to examine NWO prevalence and its associations with metabolic and immunologic measurements in a cohort of PLHIV on antiretroviral treatment (ART).Methods: ...
... Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics.On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through c ...
... During chronic viral infections, CD8 T cells rapidly lose antiviral and immune-stimulatory functions in a sustained program termed exhaustion. In addition to this loss of function, CD8 T cells with the highest affinity for viral antigen can be physically deleted. Consequently, treatments designed to restore function to exhausted cells and control chronic viral replication are limited from the onse ...
CD8-positive T-lymphocytes; COVID-19 infection; Severe acute respiratory syndrome coronavirus 2; immune response; immunoglobulins; mucins; pathogenesis; phenotype; programmed cell death
Abstract:
... During viral infection, inhibitory receptors play a key role in regulating CD8 T-cell activity. The objective of this research was to investigate programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), and CD39 exhaustion markers in CD8 T cells of new coronavirus disease-2019 (COVID-19) patients. A total of 44 patients with COVID-19 (17 subjects ...
... Pyroptosis is a recently discovered form of inflammatory programmed necrosis characterized by caspase-1-mediated and gasdermin D-dependent cell death leading to the release of pro-inflammatory cytokines such as Interleukin-1 beta (IL-1β). Here, we evaluated whether pyroptosis could be exploited in DNA vaccination by incorporating a constitutively active variant of caspase-1 to the antigen-expressi ...
... Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accesso ...
... We aimed to determine whether serum leptin levels are predictive of the occurrence of healthcare-associated infections (HAIs) in hospitalized older patients. In a prospective cohort, 232 patients had available data for leptin and were monitored for HAIs for 3 months. Admission data included comorbidities, invasive procedures, the Mini Nutritional Assessment (MNA), BMI, leptin, albumin and C-reacti ...
... BACKGROUND: Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-5 ...
... Macrophage infiltration is a hallmark of solid cancers, and overall macrophage infiltration correlates with lower patient survival and resistance to therapy. Tumor-associated macrophages, however, are phenotypically and functionally heterogeneous. Specific subsets of tumor-associated macrophage might be endowed with distinct roles on cancer progression and antitumor immunity. Here, we identify a d ...
... Tripartite-motif 21 (TRIM21) is thought to regulate the type I interferon (IFN) response to virus pathogens and serve as a cytosolic Fc receptor for immunoglobulin. Since herpes simplex virus (HSV)-1 is sensitive to type I IFN and neutralizing antibody, we investigated the role of TRIM21 in response to ocular HSV-1 infection in mice. In comparison to wild type (WT) mice, TRIM21 deficient (TRIM21 K ...
CD8-positive T-lymphocytes; homeostasis; ligands; phenotype; research
Abstract:
... T-cell responses are fine-tuned by positive and negative co-signal molecules expressed on immune cells and adjacent tissues. VSIG4 is a newly identified member of the B7 family of ligands, which negatively regulates innate inflammatory and CD4⁺ T cell-mediated responses. However, little is known about the direct effects of VSIG4, which are exerted through an unidentified counter-receptor on CD8⁺ T ...
Alireza Hassani Najafabadi; Zeynab Izadi Najaf Abadi; Marisa E. Aikins; Kathryn E. Foulds; Mitzi M. Donaldson; Wenmin Yuan; Emeka B. Okeke; Jutaek Nam; Yao Xu; Priyan Weerappuli; Taryn Hetrick; David Adams; Patrick A. Lester; Andres M. Salazar; Dan H. Barouch; Anna Schwendeman; Robert A. Seder; James J. Moon
... Conventional cancer vaccines based on soluble vaccines and traditional adjuvants have produced suboptimal therapeutic efficacy in clinical trials. Thus, there is an urgent need for vaccine technologies that can generate potent T cell responses with strong anti-tumor efficacy. We have previously reported the development of synthetic high-density protein (sHDL) nanodiscs for efficient lymph node (LN ...
Abishek Chandrashekar; Jingyou Yu; Katherine McMahan; Catherine Jacob-Dolan; Jinyan Liu; Xuan He; David Hope; Tochi Anioke; Julia Barrett; Benjamin Chung; Nicole P. Hachmann; Michelle Lifton; Jessica Miller; Olivia Powers; Michaela Sciacca; Daniel Sellers; Mazuba Siamatu; Nehalee Surve; Haley VanWyk; Huahua Wan; Cindy Wu; Laurent Pessaint; Daniel Valentin; Alex Van Ry; Jeanne Muench; Mona Boursiquot; Anthony Cook; Jason Velasco; Elyse Teow; Adrianus C.M. Boon; Mehul S. Suthar; Neharika Jain; Amanda J. Martinot; Mark G. Lewis; Hanne Andersen; Dan H. Barouch
... The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaq ...
CD8-positive T-lymphocytes; adaptive immunity; bioluminescence; genome; luciferase; mice; research
Abstract:
... CD8⁺ T cells play a critical role during adaptive immune response, which often change locations and expand or contract in numbers under different states. In the past, many attempts to develop CD8⁺T cells that express luciferase in vivo have involved the use of viral transduction, which has drawbacks of hardly tracked via detection of luciferase signal in untouched natural states. Here, we generate ...
... The response mediated by CD8⁺ T-cells in the context of infection and vaccination has been thoroughly investigated and represents one of the most important branches that allow for the development of immunity against intracellular pathogens and, thus, the establishment of robust antiviral responses. However, there is a lack of methods to assess antigen-specific CD8⁺ T-cells.Search for the ideal ass ...
... T cells can be subdivided into a number of different subsets that are defined by their distinct functions. While the specialization of different T cell subsets is partly achieved by the expression of specific genes, the overall transcriptional profiles of all T cells appear very similar. Alternative mRNA splicing is a mechanism that facilitates greater transcript/protein diversity from a limited n ...
... Somatic mutations in tumors often generate neoproteins that contain MHC-I-binding neoepitopes. Little is known if and how efficient tumor-specific neoantigens activate CD8⁺ T cells. Here, we asked whether a de novo generated neoepitope, encoded either within an otherwise conserved and ubiquitously expressed self-antigen or in a chimeric HBV core antigen expression platform, providing heterologous ...
... CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencin ...
... The vaccines currently available to control infectious bursal disease (IBD) include live-attenuated and inactivated vaccines, immune-complex vaccines, and vaccines consisting of viral constructs of herpesvirus of turkeys genetically engineered to express VP2 surface protein. To evaluate the impact of vaccines on the chicken immune system, 2 animal trials were performed in specific pathogen-free br ...
Lene S. Høydahl; Terje Frigstad; Ingunn B. Rasmussen; Inger Øynebråten; Karoline W. Schjetne; Jan Terje Andersen; Terje E. Michaelsen; Elin Lunde; Bjarne Bogen; Inger Sandlie
... Targeted delivery of antigen to antigen-presenting cells (APCs) enhances antigen presentation and thus, is a potent strategy for making more efficacious vaccines. This can be achieved by use of antibodies with specificity for endocytic surface molecules expressed on the APC. We aimed to compare two different antibody-antigen fusion modes in their ability to induce T-cell responses; first, exchange ...
CD8-positive T-lymphocytes; databases; epitopes; proteinases; vaccines; world wide web
Abstract:
... Development of an effective HIV-1 vaccine has been a great challenge faced by the research community. Recently a novel strategy targeting the viral protease cleavage sites (PCSs) has been tested and shown promising results. This T cell-based vaccine strategy depends on individuals expressing certain HLA class I molecules and since each population has unique distributions of HLA class I alleles, po ...
CD8-positive T-lymphocytes; Influenza A virus; amino acids; epitopes; mice; models; prediction; Australia
Abstract:
... Syngeneic murine systems have pre-fixed MHC, making them an imperfect model for investigating the impact of MHC polymorphism on immunodominance in influenza A virus (IAV) infections. To date, there are few studies focusing on MHC allelic differences and its impact on immunodominance even though it is well documented that an individual’s HLA plays a significant role in determining immunodominance h ...
... CD4 T cells are well known for their supportive role in CD8 T cell and B cell responses during viral infection. However, during murine cytomegalovirus (MCMV) infection in the salivary glands (SGs), CD4 T cells exhibit direct antiviral effector functions to control the infection. In this mucosal organ, opposed to other infected tissues, MCMV establishes a sustained lytic replication that lasts for ...
Luis Ontiveros-Padilla; Alberto García-Lozano; Araceli Tepale-Segura; Tania Rivera-Hernández; Rodolfo Pastelin-Palacios; Armando Isibasi; Lourdes A. Arriaga-Pizano; Laura C. Bonifaz; Constantino López-Macías
... Salmonella enterica serovar Typhi (S. Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against S. Typhi in mice and humans. Vaccination with porins induces the protection against 500 LD₅₀ of S. Typhi, life-lasting bactericidal antibodies and effector T cell responses in mice; however, the nature of the memory T cell compartment and its contribution to protection remains unk ...
... Obese visceral adipose tissue (AT) inflammation is driven by adipokine-mediated cross talk between CD8⁺ T cells and adipocytes, a process mitigated by long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) but underlying mechanisms and ensuing effects on macrophage polarization status are unknown. Using an in vitro co-culture model that recapitulates the degree of CD8⁺ T cell infiltration reported ...
... Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D ...
Priyakshi Kalita-de Croft; Haarika Chittoory; Tam H. Nguyen; Jodi M. Saunus; Woo Gyeong Kim; Amy E. McCart Reed; Malcolm Lim; Xavier M. De Luca; Kaltin Ferguson; Colleen Niland; Roberta Mazzieri; Riccardo Dolcetti; Peter T. Simpson; Sunil R. Lakhani
... The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embe ...
... H9N2 avian influenza viruses (AIV) continue to circulate in vaccinated chicken flocks in China, which prompted us to investigate the differential immune protection factors induced by H9N2 AIV infection and immunization for analyzing the reason of protection deficiency of H9N2 AIV inactivated vaccine. In this study, we firstly explored virus-induced optimal immune responses in chicken after H9N2 AI ...
... IL-15 is a member of the common gamma chain family of cytokines and plays important roles in regulating several aspects of innate and adaptive immunity. Besides its established role in controlling homeostatic proliferation and survival of memory CD8+ T cells and natural killer cells, recent findings demonstrate that inflammatory IL-15 can also stimulate a variety of effector functions, such as enh ...
... We have previously demonstrated that short-term coreceptor blockade with non-lytic monoclonal antibodies enables the long-term survival of fully allogeneic embryonic stem cell (ESC) transplants in mice. Here, we describe the use of Hu-PBL humanized mice to determine whether short-term coreceptor blockade with humanized anti-human CD4 and CD8 antibodies can achieve the same outcome towards human ES ...
... Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understandi ...
Faruku Bande; Siti Suri Arshad; Mohd Hair Bejo; Abdul Rahman Omar; Hassan Moeini; Saeid Khadkodaei; Tan Sheau Wei; Yeap Swee Keong; Yusuf Abba; Ibrahim Abubakar Anka
... Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demons ...
Hua Zhang; Wei-Lun Tang; Azadeh Kheirolomoom; Brett Z. Fite; Bo Wu; Kenneth Lau; Mo Baikoghli; Marina Nura Raie; Spencer K. Tumbale; Josquin Foiret; Elizabeth S. Ingham; Lisa M. Mahakian; Sarah M. Tam; R. Holland Cheng; Alexander D. Borowsky; Katherine W. Ferrara
... Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delive ...
... It is generally believed that a successful Zika virus (ZIKV) vaccine should induce neutralizing antibodies against the ZIKV envelope (E) protein to efficiently halt viral infection. However, E-specific neutralizing antibodies have been implicated in a phenomenon called antibody-dependent enhancement, which represents an ongoing concern in the flavivirus-vaccinology field. In this report, we invest ...
... The hypoxic microenvironment was recognized as a major driving force of the malignant phenotype in hepatocellular carcinoma (HCC), which contributes to tumour immune microenvironment (TIM) remodeling and tumor progression. Dysregulated hypoxia-related genes (HRGs) result in treatment resistance and poor prognosis by reshaping tumor cellular activities and metabolism. Approaches to identify the rel ...
... Leishmaniasis is a complex vector-borne disease mediated by Leishmania parasite and a strong and long-lasting CD4⁺ Th1 and CD8⁺-T cell immunity is required to control the infection. Thus far multivalent subunit vaccines have met this requirement more promisingly. However several full protein sequences cannot be easily arranged in one construct. Instead, new emerging immune-informatics based epitop ...
... Honey bee larva powder (HLP) has traditionally been used as a daily supplement and tonic for health promotion with an uncertain scientific basis. In this study, B16-F10 tumor-bearing mice were established to evaluate the immunomodulatory activity of HLP. The proliferation and apoptosis assays were performed to evaluate the anti-inflammatory activity of honey bee larva extract (HLE) in RAW 264.7 ma ...
CD8-positive T-lymphocytes; Forsythia suspensa; Infectious bronchitis virus; Oriental traditional medicine; active ingredients; histopathology; immunomodulation; infectious bronchitis; interleukin-2; research; therapeutics; veterinary medicine
Abstract:
... Forsythoside A is the main active ingredient in the Chinese medicine Forsythia suspensa, which has antiviral, anti-inflammatory, antioxidation, and immunoregulatory effects. It is reported that Forsythoside A can significantly inhibit the replication of the avian infectious bronchitis virus(IBV) in cells, but there is no report in chickens. The present study aimed to investigate the effect of Fors ...
Barberine A. Silatsa; Gustave Simo; Naftaly Githaka; Rolin Kamga; Farikou Oumarou; Christian Keambou Tiambo; Eunice Machuka; Jean‐Baka Domelevo; David Odongo; Richard Bishop; Jules‐Roger Kuiate; Flobert Njiokou; Appolinaire Djikeng; Roger Pelle
... A major risk factor for the spread of livestock diseases and their vectors is the uncontrolled transboundary movement of live animals for trade and grazing. Such movements constrain effective control of tick‐transmitted pathogens, including Theileria parva. Only limited studies have been undertaken to identify ticks and tick‐borne diseases (TTBDs) affecting cattle in central African countries, inc ...
... Dendritic cells (DCs) play a critical role in shaping adaptive immunity. Systemic transfer of DCs by intravenous injection has been widely investigated to inform the development of immunogenic DCs for use as cellular therapies. Adoptive transfer of DCs to mucosal sites has been limited but serves as a valuable tool to understand the role of the microenvironment on mucosal DC activation, maturation ...
... Rhynchosia nulubilis (black soybean) has many applications in oriental medicine. It is traditionally used to treat disease related with high blood pressure, diabetes, inflammation, and osteoporosis. Furthermore, fermented soybean foods have traditionally been used for immunity enhancement in East Asia. However, the anti-inflammatory effects of germinated R. nulubilis (GR) against delayed-type hype ...
... The emergence of a novel goose nephritic astrovirus (GNAstV) has caused economic losses to the Chinese goose industry. High viral load is found in the spleen of goslings infected with GNAstV, but pathological injuries to the spleen due to GNAstV are largely unknown. In this study, 50 two-day-old goslings were infected orally with GNAstV, and 50 goslings were treated with PBS as control. Spleens we ...
... The current vaccines to control bovine Babesia bigemina (B. bigemina) infection are not fully protective and vaccination failures incur heavy losses to the cattle industry around the world. Using modified micro-aerophilous stationary phase, we developed a culture-derived attenuated live vaccine against B. bigemina and tested a single subcutaneous inoculation of 2 × 10⁸ infected erythrocytes in cal ...
... The CD8 T cell response to the HLA-A2-restricted epitope LLWNGPMAV (LLW) of the non-structural protein 4b of Yellow Fever Virus (YFV) is remarkably immunodominant, highly prevalent and powerful in YFV-vaccinated humans. Here we used a combinatorial peptide library screening in the context of an A2/LLW-specific CD8 T cell clone to identify a superagonist that features a methionine to isoleucine sub ...
... The lack of useful tools for detection the impact of treatment during the follow-up of chronic Chagas disease treated patients difficult the adequate care to the affected population. The objective of this study was to evaluate the functional response of CD8⁺ T lymphocyte population, critical for the control of Trypanosoma cruzi infection, as a possible cellular biomarker of treated Chagas disease ...
... BACKGROUND: Lymphocytosis is relatively common in cats, but few studies describe lymphocyte populations or the clinical course associated with different immunophenotypic expansions. HYPOTHESIS/OBJECTIVES: We hypothesized that cats frequently develop non‐neoplastic lymphocytosis and that different neoplastic immunophenotypes have variable prognoses. We aimed to characterize the lymphocyte expansion ...
Dayane Kelly Dias do Nascimento Santos; Bárbara Rafaela da Silva Barros; Lethícia Maria de Souza Aguiar; Iranildo José da Cruz Filho; Virgínia Maria Barros de Lorena; Cristiane Moutinho Lagos de Melo; Thiago Henrique Napoleão
... In this work, we investigated the antioxidant and immunomodulatory activities of a lignin isolated from Conocarpus erectus leaves. The lignin was characterized by FTIR, ¹H NMR, ¹³C NMR and gel permeation chromatography analysis as well as ultraviolet/visible absorption spectra. The lignin was evaluated for total antioxidant activity (TAA), DPPH and ABTS⁺ scavenging abilities, and by a lipid peroxi ...
... Being a Positive sense RNA virus the recent reemergence of Chikungunya and Mayaro virus has taken the concern of the leading scientific communities of the world. Though the outbreak of Mayaro virus is limited to Neotropical region only, Chikungunya is already identified in over 60 countries around the world. Besides, the lack of a strong protective treatment, misdiagnosis issue and co-circulation ...
... The curative potential of non-autologous cellular therapy is hindered by the requirement of anti-rejection therapy. Cellular encapsulation within nondegradable biomaterials has the potential to inhibit immune rejection, but the efficacy of this approach in robust preclinical and clinical models remains poor. While the responses of innate immune cells to the encapsulating material have been charact ...
... Immunotherapy has emerged as one of the most promising treatments for cancer in recent years. However, it works only for a small proportion of patients, which can in part be attributed to the immunosuppressive tumor microenvironment (TME). Tumor associated macrophages (TAMs) are the critical components of tumors and play an important role in the development of the immunosuppressive TME. The transi ...
... Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 ...
... T cells resident within the intestinal epithelium play a central role in barrier integrity and provide a first line of immune defense. Intraepithelial T cells (IETs) are among the earliest immune cells to populate and protect intestinal tissues, thereby giving them an important role in shaping gut health early in life. In pigs, IETs are poorly defined, and their maturation in young pigs has not be ...
... Background: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. Case study: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillou ...