Bystander responses impact accurate detection of murine and human antigen-specific CD8+ T cells

Induction of memory CD8+ T cells is important for controlling infections such as malaria and HIV/AIDS and for cancer immunotherapy. Accurate assessment of antigen-specific (Ag-specific) CD8+ T cells is critical for vaccine optimization and for defining correlates of protection. However, conditions for determining Ag-specific CD8+ T cell responses ex vivo using intracellular cytokine staining (ICS) may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulation and timing of brefeldin A (BFA) addition influence the magnitude of Ag-specific and bystander T cell responses. Indeed, after immunization with an attenuated whole sporozoite malaria vaccine in humans, significantly higher numbers of IFN-γ–producing memory CD8+ T cells comprising Ag-specific and bystander responses were detected when the duration of Ag stimulation prior to addition of BFA was increased. Mechanistic analyses of virus-specific CD8+ T cells in mice revealed that the increase in IFN-γ–producing CD8+ T cells was due to bystander activation of Ag-experienced memory CD8+ T cells, and correlated with the proportion of Ag-experienced CD8+ T cells in the stimulated populations. Incubation with anti-cytokine antibodies (e.g., IL-12) improved accuracy in detecting bona fide memory CD8+ T cell responses, suggesting this as the m...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Conclusions Toxoplasma gondii infection induces a strong innate and adaptive immune response. While the innate immunity is important for controlling the early stages of the infection (Yarovinsky, 2014), the adaptive immunity is critical for restricting the parasite replication during the later stages (Gazzinelli et al., 1992). Amongst the adaptive immune subsets, CD8 T cells are the primary effector cells while CD4 T cells play an essential helper role to maintain long-term immunity (Casciotti et al., 2002). Notwithstanding, a robust CD8 T cell immunity induced during acute phase of infection, does not result in the total...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Conclusions and Perspectives It is interesting that watershed events, such as the loss of Neu5Gc from the glycocalyx of human cells have occurred numerous times in many mammalian and other vertebrate species. These cases of convergent evolution represent precious opportunities for increased understanding of evolutionary processes. In some respects, Neu5Gc is an ideal self-molecule as it is “private” to vertebrates and, based on current data, has yet to be successfully mimicked by microbes. Against the background of this benefit, the loss of Neu5Gc appears paradoxical and may implicate strong selective regimes,...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Segun Fatumo1,2,3*, Tommy Carstensen4, Oyekanmi Nashiru3, Deepti Gurdasani4†, Manjinder Sandhu4,5† and Pontiano Kaleebu1,2† 1Uganda Medical Informatics Centre, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda 2London School of Hygiene and Tropical Medicine, London, United Kingdom 3H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria 4Human Genetics, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom 5Division of Computational Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kin...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
(CNN) — From climate change to superbugs, the World Health Organization has laid out 10 big threats to our global health in 2019. And unless these threats get addressed, millions of lives will be in jeopardy. Here’s a snapshot of 10 urgent health issues, according to the United Nations’ public health agency: Not vaccinating when you can One of the most controversial recent health topics in the US is now an international concern. “Vaccine hesitancy — the reluctance or refusal to vaccinate despite the availability of vaccines — threatens to reverse progress made in tackling vaccine-prevent...
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Health News CNN Local TV Source Type: news
Instead of mind-boggling inventions, 2018 was the year when national governments, as well as healthcare regulators, started to embrace digital health technologies at scale. The year when Google, Amazon, Apple or Microsoft competed head-to-head for the biggest chunks on the healthcare market, and when the buzzword of the year award went to the blockchain. Here’s our guide to the top digital health stories from last year. 2018: Under the spell of cosmos and microcosmos Every year, The Medical Futurist team sits down and collects the top stories of the past 12 months in healthcare. We put the novelties under the microsc...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Business Future of Medicine Medical Professionals Patients Policy Makers Researchers Top Lists 2018 AI artificial intelligence artificial pancreas blockchain chatbot CRISPR deep learning diabetes digital health digital he Source Type: blogs
We’re excited to share the topic and questions for this week’s #HITsm chat happening Friday, 11/30 at Noon ET (9 AM PT). This week’s chat will be hosted by Vanessa Carter (@_FaceSA) on the topic of “The Global Impact of Health IT”. Global health pandemics like antibiotic and antimicrobial resistance are among the most critical issues to tackle and in future will require robust, harmonious data surveillance systems along with mass co-operation between the animal, human and environmental health sectors across every country [1]. This is known as One Health [2]. WHO initiatives like GLAS...
Source: EMR and HIPAA - Category: Information Technology Authors: Tags: #HITsm Healthcare Healthcare AI HealthCare IT #HITsm Topics Antibiotic Resistance GLASS Global Antimicrobial Resistance Surveillance System Global Health One Health Vanessa Carter Source Type: blogs
Abstract Emergence of drug resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected towards finding alternate chemotherapeutic agents that are capable of combating multi-drug resistant parasite strains. In the above light, scientists have come up with the concept of hybridisation of two or more active pharmacophores into a single chemical entity, resulting in 'antimalarial hybrids.' The approach has been applied widely for lead generation against deadly diseases such as cancer and AIDS, with proven potential to...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Publication date: October 2016 Source:Current Opinion in Virology, Volume 20 Author(s): Ann M Moormann, Jeffrey A Bailey Burkitt lymphoma (BL) is >90% EBV-associated when this pediatric cancer is diagnosed in regions heavily burden by endemic Plasmodium falciparum malaria and thus has been geographically classified as endemic BL. The incidence of endemic BL is 10-fold higher compared to BL diagnosed in non-malarious regions of the world. The other forms of BL have been classified as sporadic BL which contain EBV in ∼30% of cases and immunodeficiency BL which occurs in HIV-infected adults with ∼40% of tumors con...
Source: Current Opinion in Virology - Category: Virology Source Type: research
Vaccination is one of the cheapest health-care interventions that have saved more lives than any other drugs or therapies. Due to successful immunization programs we rarely hear about some of the common diseases of the early twentieth century including small pox and polio. Vaccination programs have also helped to increase food production notably poultry, cattle, and milk production due to lower incidence of infectious diseases in farm animals. Though vaccination programs have eradicated several diseases and increased the quality of life there are several diseases that have no effective vaccines. Currently there are no vacc...
Source: Springer protocols feed by Immunology - Category: Allergy & Immunology Source Type: news
Conclusions Patterns of disease are changing rapidly in LMICs. Pollution-related chronic diseases are becoming more common. This shift presents a particular problem for children, who are proportionately more heavily exposed than are adults to environmental pollutants and for whom these exposures are especially dangerous. Better quantification of environmental exposures and stepped-up efforts to understand how to prevent exposures that cause disease are needed in LMICs and around the globe. To confront the global problem of disease caused by pollution, improved programs of public health monitoring and environmental protecti...
Source: EHP Research - Category: Environmental Health Authors: Tags: Brief Communication March 2016 Source Type: research
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