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https://www.readbyqxmd.com/read/29144460/inflammation-induced-iga-cells-dismantle-anti-liver-cancer-immunity
#1
Shabnam Shalapour, Xue-Jia Lin, Ingmar N Bastian, John Brain, Alastair D Burt, Alexander A Aksenov, Alison F Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T Yu, Ronald M Evans, Pieter C Dorrestein, Rob Knight, Christopher Benner, Quentin M Anstee, Michael Karin
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA(+)) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8(+) T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29140228/co-factor-independent-phosphoglycerate-mutase-of-leishmania-donovani-modulates-macrophage-signalling-and-promotes-t-cell-repertoires-bearing-epitopes-for-both-mhc-i-and-mhc-ii
#2
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
https://www.readbyqxmd.com/read/29138980/cd28-neg-t-lymphocytes-of-a-melanoma-patient-harbor-tumor-immunity-and-a-high-frequency-of-germline-encoded-and-public-tcrs
#3
Hisayoshi Hashimoto, Marco Sterk, Karin Schilbach
Increased numbers of CD8(+)CD28(neg.) T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8(+)CD28(neg.) T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28(neg.) T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status...
November 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29138313/t-cell-receptor-sequencing-of-early-stage-breast-cancer-tumors-identifies-altered-clonal-structure-of-the-t-cell-repertoire
#4
John F Beausang, Amanda J Wheeler, Natalie H Chan, Violet R Hanft, Frederick M Dirbas, Stefanie S Jeffrey, Stephen R Quake
Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-post-depletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#5
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevents CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable of repopulating post-depletion than more naïve phenotypes, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29134198/%C3%AF-3-polyunsaturated-fatty-acids-direct-differentiation-of-the-membrane-phenotype-in-mesenchymal-stem-cells-to-potentiate-osteogenesis
#6
Kandice R Levental, Michal A Surma, Allison D Skinkle, Joseph H Lorent, Yong Zhou, Christian Klose, Jeffrey T Chang, John F Hancock, Ilya Levental
Mammalian cells produce hundreds of dynamically regulated lipid species that are actively turned over and trafficked to produce functional membranes. These lipid repertoires are susceptible to perturbations from dietary sources, with potentially profound physiological consequences. However, neither the lipid repertoires of various cellular membranes, their modulation by dietary fats, nor their effects on cellular phenotypes have been widely explored. We report that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts or adipocytes results in extensive remodeling of the plasma membrane (PM), producing cell-specific membrane compositions and biophysical properties...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#7
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123524/vertebrate-adaptive-immunity-comparative-insights-from-a-teleost-model
#8
REVIEW
Harry W Dickerson, Robert Craig Findly
The channel catfish (Ictalurus punctatus) and the ciliated protozoan parasite Ichthyophthirius multifiliis are used to study pathogen-specific protective immunity. In this review, we briefly describe this host-parasite system and discuss the comparative insights it provides on the adaptive immune response of vertebrates. We include studies related to cutaneous mucosal immunity, B cell memory responses, and analyses of αβ T cell receptor (TCR) repertoires. This host-parasite model has played an important role in elucidating host protective responses to parasite invasion and for comparative studies of vertebrate immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123465/autoimmunity-as-a-driving-force-of-cognitive-evolution
#9
Serge Nataf
In the last decades, increasingly robust experimental approaches have formally demonstrated that autoimmunity is a physiological process involved in a large range of functions including cognition. On this basis, the recently enunciated "brain superautoantigens" theory proposes that autoimmunity has been a driving force of cognitive evolution. It is notably suggested that the immune and nervous systems have somehow co-evolved and exerted a mutual selection pressure benefiting to both systems. In this two-way process, the evolutionary-determined emergence of neurons expressing specific immunogenic antigens (brain superautoantigens) has exerted a selection pressure on immune genes shaping the T-cell repertoire...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29122948/microrna-regulation-of-type-2-innate-lymphoid-cell-homeostasis-and-function-in-allergic-inflammation
#10
Priti B Singh, Heather H Pua, Hannah C Happ, Christoph Schneider, Jakob von Moltke, Richard M Locksley, Dirk Baumjohann, K Mark Ansel
MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29112951/phenotype-and-specificity-of-t-cells-in-primary-human-cytomegalovirus-infection-during-pregnancy-il-7rpos-long-term-memory-phenotype-is-associated-with-protection-from-vertical-transmission
#11
Federico Mele, Chiara Fornara, David Jarrossay, Milena Furione, Alessia Arossa, Arsenio Spinillo, Antonio Lanzavecchia, Giuseppe Gerna, Federica Sallusto, Daniele Lilleri
Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins...
2017: PloS One
https://www.readbyqxmd.com/read/29109146/peptide-splicing-by-the-proteasome
#12
Nathalie Vigneron, Violette Ferrari, Vincent Stroobant, Joanna Abi Habib, Benoit Van den Eynde
The proteasome is the major protease responsible for the production of antigenic peptides recognized by CD8+ cytolytic T cells (CTL). These peptides, generally 8-to-10 amino acid-long, are presented at the cell surface by major histocompatibility complex (MHC) class I molecules. Although for years, these peptides were believed to solely derive from linear fragments of proteins, this concept was challenged several years ago by the isolation of anti-tumor CTL that recognized spliced peptides, i.e. peptides composed of fragments originally distant in the parental protein...
November 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29106696/the-mechanisms-shaping-the-repertoire-of-cd4-foxp3-treg-cells
#13
REVIEW
Piotr Kraj, Leszek Ignatowicz
Regulatory T (Treg ) cells expressing Foxp3 transcription factor control homeostasis of the immune system, antigenic responses to commensal and pathogenic microbiota, and immune responses to self and tumor antigens. Treg cells differentiate in the thymus, (tTreg ) along with conventional CD4(+) T cells, in processes of positive and negative selection. Another class of Treg cells is generated in peripheral tissues (pTreg ) by inducing Foxp3 expression in conventional CD4(+) T cells in response to antigenic stimulation...
November 6, 2017: Immunology
https://www.readbyqxmd.com/read/29103899/perturbation-of-the-t-cell-receptor-repertoire-occurs-with-increasing-age-in-dogs
#14
Angela Holder, Samantha M Mirczuk, Robert C Fowkes, Donald B Palmer, Richard Aspinall, Brian Catchpole
Immunosenescence is the gradual deterioration in immune system function associated with ageing. This decline is partly due to involution of the thymus, which leads to a reduction in the output of naive T cells into the circulating lymphocyte pool. Expansion of existing naive and memory T cell populations, to compensate for the reduction in thymic output, can lead to reduced diversity in the T cell repertoire with increasing age, resulting in impairment of immune responses to novel antigenic challenges, such as during infection and vaccination...
October 28, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29102863/negative-selection-epitope-mimicry-and-autoimmunity
#15
REVIEW
Noel R Rose
Infections often precede the onset of autoimmune disease and molecular (or epitope) mimicry is a plausible link. Cross-reacting epitopes are common between an infecting microorganism and the host because negative selection of self-reactive T-cells and B-cells is frequently incomplete. Complete eradication could lead to major voids in the immunologic repertoire. The association of an autoimmune disease with a microbial epitope may signify a causal relationship with the organism, an indirect connection through bystander effects, persistent infection or coincidence...
November 2, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29101015/dna-damage-metabolism-and-aging-in-pro-inflammatory-t-cells-rheumatoid-arthritis-as-a-model-system
#16
REVIEW
Yinyin Li, Jörg J Goronzy, Cornelia M Weyand
The aging process is the major driver of morbidity and mortality, steeply increasing the risk to succumb to cancer, cardiovascular disease, infection and neurodegeneration. Inflammation is a common denominator in age-related pathologies, identifying the immune system as a gatekeeper in aging overall. Among immune cells, T cells are long-lived and exposed to intense replication pressure, making them sensitive to aging-related abnormalities. In successful T cell aging, numbers of naïve cells, repertoire diversity and activation thresholds are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and pro-inflammatory effector cells are enriched...
November 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29080364/comparative-analysis-of-murine-t-cell-receptor-repertoires
#17
REVIEW
Mark Izraelson, Tatiana O Nakonechnaya, Bruno Moltedo, Evgeniy S Egorov, Sofya A Kasatskaya, Ekaterina V Putintseva, Ilgar Z Mamedov, Dmitriy B Staroverov, Irina I Shemiakina, Maria Y Zakharova, Alexey N Davydov, Dmitriy A Bolotin, Mikhail Shugay, Dmitriy M Chudakov, Alexander Y Rudensky, Olga V Britanova
On the way of understanding the rules and laws of adaptive immunity, high-throughput profiling of TCR repertoires becomes a powerful tool. The structure of TCR repertoires is insightful and instructive even before antigen specificity of each particular receptor becomes available. It embodies information about the thymic and peripheral selection of T cells, about the readiness of an adaptive immunity to withstand new challenges, about the character, the magnitude, and the memory of immune response, and about the etiological and functional proximity of T cell subsets...
October 28, 2017: Immunology
https://www.readbyqxmd.com/read/29075258/quantitative-characterization-of-the-t-cell-receptor-repertoire-of-na%C3%A3-ve-and-memory-subsets-using-an-integrated-experimental-and-computational-pipeline-which-is-robust-economical-and-versatile
#18
Theres Oakes, James M Heather, Katharine Best, Rachel Byng-Maddick, Connor Husovsky, Mazlina Ismail, Kroopa Joshi, Gavin Maxwell, Mahdad Noursadeghi, Natalie Riddell, Tabea Ruehl, Carolin T Turner, Imran Uddin, Benny Chain
The T cell receptor (TCR) repertoire can provide a personalized biomarker for infectious and non-infectious diseases. We describe a protocol for amplifying, sequencing, and analyzing TCRs which is robust, sensitive, and versatile. The key experimental step is ligation of a single-stranded oligonucleotide to the 3' end of the TCR cDNA. This allows amplification of all possible rearrangements using a single set of primers per locus. It also introduces a unique molecular identifier to label each starting cDNA molecule...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29073905/therapeutic-application-of-t-regulatory-cells-in-composite-tissue-allotransplantation
#19
REVIEW
Jeong-Hee Yang, Seok-Chan Eun
With growing number of cases in recent years, composite tissue allotransplantation (CTA) has been improving the quality of life of patient who seeks reconstruction and repair of damaged tissues. Composite tissue allografts are heterogeneous. They are composed of a variety of tissue types, including skin, muscle, vessel, bone, bone marrow, lymph nodes, nerve, and tendon. As a primary target of CTA, skin has high antigenicity with a rich repertoire of resident cells that play pivotal roles in immune surveillance...
October 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29067686/association-between-gm-hla-and-killer-immunoglobulin-like-receptors-and-the-natural-course-of-hcmv-infection-a-pilot-study-performed-in-sicilian-population
#20
Danilo Di Bona, Giulia Accardi, Anna Aiello, Massimo Bilancia, Giuseppina Candore, Claudia Colomba, Calogero Caruso, Giovanni Duro, Caterina M Gambino, Luigi Macchia, Janardan P Pandey
Natural killer (NK) cells provide a major defence against cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. Also GM allotypes, able to influence the NK antibody-dependent cell-mediated cytotoxicity (ADCC), appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA...
October 25, 2017: Immunology
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