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T cell memory

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https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#1
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28323492/regulatory-and-exhausted-t-cell-responses-to-aav-capsid
#2
Gwladys Gernoux, James M Wilson, Christian Mueller
Recombinant adeno-associated viruses are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting Hemophilia B patients 10 years ago, immune responses to AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells which have correlated with a decline in AAV transduced tissue in some patients...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28323147/increase-of-circulating-%C3%AE-4%C3%AE-7-conventional-memory-cd4-and-regulatory-t-cells-in-patients-with-common-variable-immunodeficiency-cvid
#3
Karina Mescouto de Melo, Susanne Unger, Baerbel Keller, Sylvia Gutenberger, Ina Stumpf, Sigune Goldacker, Klaus Warnatz
This study investigated whether circulating α4β7(+) expressing T cells could serve as a potential marker for gastrointestinal (GI) disease activity in patients with CVID. The analysis of α4β7(+) T cells in the peripheral blood of 36 patients and 22 healthy donors (HD) revealed increased percentages of α4β7(+) conventional memory CD4 T cells and Tregs, but not among CD8 T-cell populations in patients with CVID compared to HD. No differences between patients with and without chronic or acute GI symptoms were observed...
March 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28322863/deep-immune-profiling-by-mass-cytometry-links-human-t-and-nk-cell-differentiation-and-cytotoxic-molecule-expression-patterns
#4
Bertram Bengsch, Takuya Ohtani, Ramin Sedaghat Herati, Niels Bovenschen, Kyong-Mi Chang, E John Wherry
The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer...
March 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28320841/prefrontal-cortex-kca2-channels-regulate-mglu5-dependent-plasticity-and-extinction-of-alcohol-seeking-behavior
#5
Reginald Cannady, Justin T McGonigal, Ryan J Newsom, John J Woodward, Patrick J Mulholland, Justin T Gass
Identifying novel treatments that facilitate extinction learning could enhance cue-exposure therapy and reduce high relapse rates in alcoholics. Activation of mGlu5 receptors in the infralimbic prefrontal cortex (IL-PFC) facilitates learning during extinction of cue-conditioned alcohol-seeking behavior. Small-conductance calcium-activated potassium (KCa2) channels have also been implicated in extinction learning of fear memories, and mGlu5 receptor activation can reduce KCa2 channel function. Using a combination of electrophysiological, pharmacological, and behavioral approaches, this study examined KCa2 channels as a novel target to facilitate extinction of alcohol-seeking behavior in rats...
March 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28320753/do-memory-b-cells-form-secondary-germinal-centers-impact-of-antibody-class-and-quality-of-memory-t-cell-help-at-recall
#6
Louise J McHeyzer-Williams, Chad Dufaud, Michael G McHeyzer-Williams
Antigen recall can clearly induce a germinal center (GC) reaction. What has become an issue for debate are the origins of the antigen-specific B cells that form memory-response GCs (mGCs). Using antigen labeling and adoptive transfer, memory B cells expressing different antibody class can give rise to mGCs with differing efficiency. Here, we will argue that the range of class-specific memory responses reported across multiple systems represents the spectrum of memory B-cell fate and function. While the formulation of recall immunogen and location of mGCs have an important role, we propose that effective cognate regulation is the key variable influencing recall outcome...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320269/status-epilepticus-impairs-synaptic-plasticity-in-rat-hippocampus-and-is-followed-by-changes-in-expression-of-nmda-receptors
#7
T Y Postnikova, O E Zubareva, A A Kovalenko, K K Kim, L G Magazanik, A V Zaitsev
Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319732/an-antigen-to-remember-regulation-of-b-cell-memory-in-health-and-disease
#8
REVIEW
Aleta Pupovac, Kim L Good-Jacobson
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#9
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#10
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28318628/b-and-t-cell-subpopulations-in-patients-with-severe-idiopathic-membranous-nephropathy-may-predict-an-early-response-to-rituximab
#11
Michelle Rosenzwajg, Eva Languille, Hanna Debiec, Joana Hygino, Karine Dahan, Tabassome Simon, David Klatzmann, Pierre Ronco
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56(bright)CD16(-/lo) NK subset...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#12
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316598/t-cell-receptor-and-cytokine-signaling-can-function-at-different-stages-to-establish-and-maintain-transcriptional-memory-and-enable-t-helper-cell-differentiation
#13
REVIEW
Sarah L Bevington, Pierre Cauchy, David R Withers, Peter J L Lane, Peter N Cockerill
Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#14
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28303138/importance-of-salmonella-typhi-responsive-cd8-t-cell-immunity-in-a-human-typhoid-fever-challenge-model
#15
Stephanie Fresnay, Monica A McArthur, Laurence S Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Typhoid fever, caused by the human-restricted organism Salmonella enterica serovar Typhi (S. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models. Herein, we report that high levels of S. Typhi-responsive CD8+ T cells at baseline significantly correlate with an increased risk of disease in humans challenged with a high dose (~10(4) CFU) wild-type S. Typhi. Typhoid fever development was associated with higher multifunctional S...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#16
Rory T Coleman, Gary Struhl
Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28300170/cd8-t-cells-specific-for-the-islet-autoantigen-igrp-are-restricted-in-their-t-cell-receptor-chain-usage
#17
Yannick F Fuchs, Anne Eugster, Sevina Dietz, Christian Sebelefsky, Denise Kühn, Carmen Wilhelm, Annett Lindner, Anita Gavrisan, Jan Knoop, Andreas Dahl, Anette-G Ziegler, Ezio Bonifacio
CD8(+) T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8(+) T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8(+) T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer(+) CD8(+) T cells representing 48 clonotypes were obtained...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298421/mimicry-of-an-hiv-broadly-neutralizing-antibody-epitope-with-a-synthetic-glycopeptide
#18
S Munir Alam, Baptiste Aussedat, Yusuf Vohra, R Ryan Meyerhoff, Evan M Cale, William E Walkowicz, Nathan A Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G Reed, Mark Louder, Robert T Bailer, Lynn Morris, Salim S Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C Montefiori, Peter K Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B Kepler, Kevin O Saunders, Joseph Sodroski, Peter D Kwong, John R Mascola, Mattia Bonsignori, M Anthony Moody, Samuel Danishefsky, Barton F Haynes
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28298290/a-prime-boost-pfcs14k-m-mva-spfcs-m-vaccination-protocol-generates-robust-cd8-t-cell-and-antibody-responses-to-plasmodium-falciparum-circumsporozoite-protein-and-protects-mice-against-malaria
#19
Aneesh Vijayan, Ernesto Mejías-Pérez, Diego A Espinosa, Suresh C Raman, Carlos Oscar S Sorzano, Fidel Zavala, Mariano Esteban
Vaccines against the pre-erythrocytic stages of malaria are appealing, since the parasite can be eliminated before disease onset and since they offer the unique possibility of targeting the parasite with both antibodies and T cells. Although the role CD8(+) T cells in pre-erythrocytic malaria stages is well documented, a highly effective T cell-inducing vaccine remains to be advanced. Here we report the development of a prime-boost immunization regimen with the Plasmodium falciparum circumsporozoite protein (PfCS) fused to the oligomer-forming vaccinia virus A27 protein and a modified vaccinia virus Ankara (MVA) vector expressing PfCS...
March 15, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28295779/allergic-disease-in-8-year-old-children-is-preceded-by-delayed-b-cell-maturation
#20
Anna Strömbeck, Inger Nordström, Kerstin Andersson, Helen Andersson, Susanne Johansen, Cristina Maglio, Hardis Rabe, Ingegerd Adlerberth, Agnes E Wold, Bill Hesselmar, Anna Rudin, Anna-Carin Lundell
BACKGROUND: We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5(+) B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age. OBJECTIVE: To examine if B- and T-cell maturation are associated with allergic disease and farming environment over the first 8 years in life. METHODS: In the prospective FARMFLORA study, including both farming and non-farming families, 48 out of 65 children took part in the 8-year follow-up study...
March 14, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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