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Immunology

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https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#1
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28628194/signals-that-drive-t-follicular-helper-cell-formation
#2
REVIEW
Louise M C Webb, Michelle A Linterman
T follicular helper (TFH) cells are a distinct type of CD4+ T cell specialized in providing help to B cells during the germinal center (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of TFH cells can result in autoimmunity whilst too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate, but limited, help to B cells. Unlike the majority of other CD4+ T cell subsets, TFH cell differentiation occurs in three phases defined by their anatomical location...
June 19, 2017: Immunology
https://www.readbyqxmd.com/read/28621843/metabolic-reprogramming-in-the-tumour-microenvironment-a-hallmark-shared-by-cancer-cells-and-t-lymphocytes
#3
REVIEW
Katrina E Allison, Brenda L Coomber, Byram W Bridle
Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and upregulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system...
June 16, 2017: Immunology
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#4
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28617945/microrna-cluster-106a-363-is-involved-in-t-helper-17-th17-cell-differentiation
#5
Marc Kaestle, Sabine Bartel, Kerstin Geillinger-Kästle, Martin Irmler, Johannes Beckers, Bernhard Ryffel, Oliver Eickelberg, Susanne Krauss-Etschmann
T-helper cell 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct Th subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signaling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine Th cell differentiation by combining Affymetrix mRNA and miRNA arrays and in-silico analysis...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28617936/t-follicular-regulatory-cells-in-mice-and-men
#6
REVIEW
Ana Raquel Maceiras, Valter R Fonseca, Ana Agua-Doce, Luis Graca
It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal center (GC) reaction where affinity maturation and isotype switching occurs. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously, presenting simultaneously characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression)...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28582800/regulation-of-cd4-t-cells-and-their-effects-on-immunopathological-inflammation-following-viral-infection
#7
Mitra Bhattacharyya, Patrick Madden, Nathan Henning, Shana Gregory, Malika Aid, Amanda Martinot, Dan H Barouch, Pablo Penaloza-MacMaster
CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naïve CD4 T cells undergo substantial expansion following infection, but can induce lethal TH1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper (Tfh) cell subsets and were able to improve adaptive immune responses in the context of minimal tissue damage...
June 5, 2017: Immunology
https://www.readbyqxmd.com/read/28581024/blomia-tropicalis-allergen-5-blo-t-5-t-cell-epitopes-and-their-ability-to-suppress-the-allergic-immune-response
#8
Kenneth H Wong, Qian Zhou, Nayana Prabhu, Kazuki Furuhashi, Yen Leong Chua, Gijsbert M Grotenbreg, David M Kemeny
Blomia tropicalis is the major asthma allergen in the tropics comparable to Dermatophagoides pteronyssinus. However, little is known about the B tropicalis epitopes recognized by T cells. Our aim was to identify the T cell epitopes in the major B tropicalis allergen, Blo t 5, and investigate the potential of the corresponding peptides to inhibit the allergic inflammatory lung response. C57BL/6 mice were immunized with plasmid DNA encoding Blo t 5 and T cell epitopes identified using the IFN-γ ELISPOT assay with 15-mer overlapping peptides...
June 5, 2017: Immunology
https://www.readbyqxmd.com/read/28580688/t-cell-regulation-through-a-basic-suppressive-mechanism-targeting-low-density-lipoprotein-receptor-related-protein-1
#9
Jeneen Panezai, Eva Bergdahl, Karl-Gösta Sundqvist
Cell adhesion is generally considered to depend on positive regulation through ligation of integrins and cytokine receptors. However, here we show that T cell adhesion, and notably also TCR-induced activation, are subject to constant suppression through shedding of low density lipoprotein receptor-related protein1 (LRP1). The broad-spectrum metalloprotease inhibitor GM6001 abrogated shedding thus inducing prominent cell surface expression of LRP1 while enhancing TCR-induced activation and adhesion to β1 and β2 integrin ligands, hence arresting the cells...
June 5, 2017: Immunology
https://www.readbyqxmd.com/read/28564390/development-of-an-epitope-panel-for-consistent-identification-of-antigen-specific-t-cells-in-humans
#10
Andreas Fløe, Caroline Løppke, Ole Hilberg, Christian Wejse, Liselotte Brix, Kivin Jacobsen
OBJECTIVE: We aimed to establish a panel of MHC-peptide multimers suitable as a positive control in detection of HLA A*0201 restricted antigen specific T-cells (ASTC) by flow cytometry. MATERIALS AND METHODS: MHC Dextramers were loaded with HLA A*0201 binding peptides from viral antigens and melanoma targets identified from a literature search and in-silico prediction. Peripheral blood mononuclear cells (PBMC) from healthy donors were analysed with the MHC Dextramers using flow cytometry...
May 31, 2017: Immunology
https://www.readbyqxmd.com/read/28557002/mtorc1-signaling-is-essential-for-germinal-center-reaction
#11
Bingshou Li, Zhirong Li, Pengcheng Wang, Qizhao Huang, Lifan Xu, Ran He, Lilin Ye, Qiang Bai
The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that has been shown to be essential for the differentiation and function of various immune cells. Earlier in vitro studies showed that mTOR signaling regulates B cell biology by supporting their activation and proliferation. However, how mTOR signaling temporally regulates in vivo germinal center B (GCB) cell development and differentiation into short-lived plasma cells, long-lived plasma cells and memory cells is still not well understood...
May 30, 2017: Immunology
https://www.readbyqxmd.com/read/28556970/topical-treatment-of-all-trans-retinoic-acid-inhibits-murine-melanoma-partly-by-promoting-cd8-t-cell-immunity
#12
Wei Yin, Yan Song, Qing Liu, Yunyun Wu, Rui He
All-trans retinoic acid (atRA), the main biologically active metabolite of vitamin A, has been implicated in immunoregulation and anti-cancer. A recent finding that vitamin A could decrease the risk of melanoma in human indicates the beneficial role of atRA in melanoma. However, it remains unknown whether topical application of atRA could inhibit melanoma growth by influencing tumor immunity. We here demonstrated topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth...
May 30, 2017: Immunology
https://www.readbyqxmd.com/read/28556921/membrane-bound-dickkopf-1-in-foxp3-regulatory-t-cells-suppresses-t-cell-mediated-autoimmune-colitis
#13
Wook-Jin Chae, Jong-Hyun Park, Octavian Henegariu, Saliha Yilmaz, Liming Hao, Alfred L M Bothwell
Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3(+) regulatory T cells (Treg cells) utilize Dickkopf-1 (DKK-1) to regulate T cell-mediated tolerance in the T cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4(+) T cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymic-derived Treg cells showed a robust expression of DKK-1 but not in naïve or effector CD4 T cells...
May 30, 2017: Immunology
https://www.readbyqxmd.com/read/28556916/intestinal-dysbiosis-and-probiotic-applications-in-autoimmune-diseases
#14
REVIEW
Gislane Lelis Vilela de Oliveira, Aline Zazeri Leite, Bruna Stevanato Higuchi, Marina Ignácio Gonzaga, Vânia Sammartino Mariano
In humans, a complex interaction between the host immune system and commensal microbiota is required to maintain gut homeostasis. In this symbiotic relationship, the microbiota provides carbohydrate fermentation and digestion, vitamin synthesis, and gut-associated lymphoid tissue development, as well as prevents colonization by pathobionts, whereas the host offers a niche and nutrients for the survival of the microbiota. However, when this mutualistic relationship is compromised and an altered interaction between immune cells and microorganisms occurs, the gut microbiota may cause or contribute to the establishment of infectious diseases and trigger autoimmune diseases...
May 29, 2017: Immunology
https://www.readbyqxmd.com/read/28555812/lung-resident-%C3%AE-%C3%AE-t-cells-and-their-roles-in-lung-diseases
#15
REVIEW
Min Cheng, Shilian Hu
γδ T cells are greatly enriched in mucosal and epithelial sites, such as the skin, respiratory, digestive and reproductive tracts, and they are defined as tissue-resident immune cells. In these tissues, the characteristics and biological roles of γδ T cells are distinguished from each other. The lungs represent the most challenging immunological dilemma for the host, and they have their own effective immune system. The abundance of γδ T cells, an estimated 8-20% of resident pulmonary lymphocytes in the lung, maintains lung tissue homeostasis...
May 29, 2017: Immunology
https://www.readbyqxmd.com/read/28542831/machine-learning-reveals-a-non-canonical-mode-of-peptide-binding-to-mhc-class-ii-molecules
#16
Massimo Andreatta, Vanessa Isabell Jurtz, Thomas Kaever, Alessandro Sette, Bjoern Peters, Morten Nielsen
MHC class II molecules play a fundamental role in the cellular immune system: they load short peptide fragments derived from extracellular proteins and present them on the cell surface. It is currently thought that the peptide binds lying more or less flat in the MHC groove, with a fixed distance of nine amino acids between the first and last residue in contact with the MHCII. While confirming that the great majority of peptides bind to the MHC using this canonical mode, we report evidence for an alternative, less common mode of interaction...
May 24, 2017: Immunology
https://www.readbyqxmd.com/read/28543817/influence-of-diabetes%C3%A2-mellitus-on-the-immunity-to-human-tuberculosis
#17
REVIEW
Nathella Pavan Kumar, Subash Babu
Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, with development of DM pandemic in countries where tuberculosis (TB) is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility...
May 22, 2017: Immunology
https://www.readbyqxmd.com/read/28542929/the-immune-response-to-prevotella-bacteria-in-chronic-inflammatory-disease
#18
REVIEW
Jeppe Madura Larsen
The microbiota plays a central role in human health and disease by shaping immune development, immune responses, metabolism, and protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease modulating bacteria. Emerging studies in humans have linked increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders, and low-grade systemic inflammation...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28542921/cd40-mediated-signaling-influences-trafficking-tcr-expression-and-t-cell-pathogenesis-in-the-nod-model-of-type-1-diabetes
#19
Gisela M Vaitaitis, Dan M Waid, Martin G Yussman, David H Wagner
CD40 plays a critical role in the pathogenesis of type 1 diabetes (T1D). The mechanism of action however is undetermined, likely because CD40 expression has been grossly underestimated. CD40 is expressed on numerous cell types that now include T cells and pancreatic β cells. CD40(+) CD4(+) cells (TH40) prove highly pathogenic in NOD mice and in translational human T1D studies. We generated BDC2.5.CD40(-/-) and re-derived NOD.CD154(-/-) mice to better understand CD40 mechanism of action. Fully functional CD40 expression is required not only for T1D development but for insulitis...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#20
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
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