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https://www.readbyqxmd.com/read/29166579/the-tcr-takes-some-immune-responsibility
#1
Ashley A Viehmann Milam, Paul M Allen
In this issue of Immunity, Van Braeckel-Budimmir et al. (2017) reveal that the pathogenic response of mice to a Plasmodium berghei infection is dominated by a Vβ8.1 T cell response. Mice lacking Vβ8.1 T cells fail to mount a pathogenic response, thus showing that the TCR locus can be an Immune response (Ir) gene.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29165988/bioconjugate-strategies-for-the-induction-of-antigen-specific-tolerance-in-autoimmune-diseases
#2
Chunsong Yu, Jingchao Xi, Meng Li, Myunggi An, Haipeng Liu
Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases...
November 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29164800/the-generation-of-human-%C3%AE-%C3%AE-t-cell-derived-induced-pluripotent-stem-cells-from-whole-peripheral-blood-mononuclear-cell-culture
#3
Daisuke Watanabe, Michiyo Koyanagi-Aoi, Mariko Taniguchi-Ikeda, Yukiko Yoshida, Takeshi Azuma, Takashi Aoi
γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti-tumor activities are exerted through several different pathways in a MHC-unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T-cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T-cell receptor (TCR) genes as their original T-cells, which provide nearly limitless sources for antigen-specific cytotoxic T lymphocytes (CTLs)...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29163767/immunology-repertoire-study-of-pulmonary-sarcoidosis-t-cells-in-cd4-cd8-pbmc-and-tissue
#4
Yingyun Fu, Yazhen Li, Lan Xu, Shengguo Liu, Minlian Wang, Lu Xiao, Song Liu, Yong Dai
Sarcoidosis is a systemic granulomatous disorder highly related with immune response. The diversity and stability of the immune system could be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (TCR). Here we used a combination of multiplex PCR and next-generation sequencing to conduct a good quality analysis of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from 7 sarcoidosis patients and lung sarcoidosis tissue from 6 patients...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163518/mixed-signals-co-stimulation-in-invariant-natural-killer-t-cell-mediated-cancer-immunotherapy
#5
REVIEW
Susannah C Shissler, Michael S Lee, Tonya J Webb
Invariant natural killer T (iNKT) cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162920/the-corepressor-ncor1-regulates-the-survival-of-single-positive-thymocytes
#6
Lena Müller, Daniela Hainberger, Valentina Stolz, Patricia Hamminger, Hammad Hassan, Teresa Preglej, Nicole Boucheron, Shinya Sakaguchi, G Jan Wiegers, Andreas Villunger, Johan Auwerx, Wilfried Ellmeier
Nuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells is not known. Here we show that Cd4-Cre-mediated deletion of NCOR1 (NCOR1 cKO(Cd4)) resulted in a reduction of peripheral T cell numbers due to a decrease in single-positive (SP) thymocytes. In contrast, double-positive (DP) thymocyte numbers were not affected in the absence of NCOR1. The reduction in SP cells was due to diminished survival of NCOR1-null postselection TCRβ(hi)CD69(+) and mature TCRβ(hi)CD69(-) thymocytes...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158404/cd1b-restricted-gem-t-cell-responses-are-modulated-by-mycobacterium-tuberculosis-mycolic-acid-meromycolate-chains
#7
Andrew Chancellor, Anna S Tocheva, Chris Cave-Ayland, Liku Tezera, Andrew White, Juma'a R Al Dulayymi, John S Bridgeman, Ivo Tews, Susan Wilson, Nikolai M Lissin, Marc Tebruegge, Ben Marshall, Sally Sharpe, Tim Elliott, Chris-Kriton Skylaris, Jonathan W Essex, Mark S Baird, Stephan Gadola, Paul Elkington, Salah Mansour
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29155103/rasgrp1-mutation-in-autoimmune-lymphoproliferative-syndrome-like-disease
#8
Huawei Mao, Wanling Yang, Sylvain Latour, Jing Yang, Sarah Winter, Jian Zheng, Ke Ni, Minmin Lv, Chenjing Liu, Hongmei Huang, Koon-Wing Chan, Pamela Pui-Wah Lee, Wenwei Tu, Alain Fischer, Yu-Lung Lau
BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of lymphocyte homeostasis due to impaired apoptosis. It was initially regarded as a very rare disease, but recent studies show it may be more common than previously thought. Defects in a couple of genes have been identified in a proportion of ALPS patients, but around one third of such patients remain undefined genetically. OBJECTIVE: We described two siblings presenting with ALPS-like disease...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29154771/in-vitro-blockade-of-the-cd4-receptor-co-signal-in-antigen-specific-t-cell-stimulation-cultures-induces-the-outgrowth-of-potent-cd4-independent-t-cell-effectors
#9
Sarah Vatter, Maximilian Schmid, Claudia Gebhard, Carina Mirbeth, Sebastian Klobuch, Michael Rehli, Wolfgang Herr, Simone Thomas
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus. Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach...
November 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29152796/the-genetic-basis-of-seborrheic-dermatitis-a-review
#10
REVIEW
Marko A Karakadze, Penelope A Hirt, Tongyu C Wikramanayake
Seborrheic Dermatitis (SD) is a common inflammatory skin disease that presents as itchy, flaking skin in the seborrheic areas. Various environmental and intrinsic factors have been identified as predisposing factors for SD, but its etiology remains poorly understood. Although it was recognized that genetic factors play a role in SD etiology, there have not been studies that systematically review the literature specifically for causal mutations or protein deficiencies in SD. In this review, we searched various databases for gene mutations and protein deficiencies that cause SD or SD-like phenotype in humans and experimental animals, and summarize 11 gene mutations or protein deficiencies that were described in the literature...
November 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29152058/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#11
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151581/human-pbmc-transferred-murine-mhc-class-i-ii-deficient-nog-mice-enable-long-term-evaluation-of-human-immune-responses
#12
Tomonori Yaguchi, Asuka Kobayashi, Takashi Inozume, Kenji Morii, Haruna Nagumo, Hiroshi Nishio, Takashi Iwata, Yuyo Ka, Ikumi Katano, Ryoji Ito, Mamoru Ito, Yutaka Kawakami
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg(null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#13
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29147589/%C3%AE-%C3%AE-t-cell-acute-lymphoblastic-leukemia-lymphoma-discussion-of-two-pediatric-cases-and-its-distinction-from-other-mature-%C3%AE-%C3%AE-t-cell-malignancies
#14
Eric X Wei, Vasiliki Leventaki, John K Choi, Susana C Raimondi, Elizabeth M Azzato, Sheila A Shurtleff, Menchu G Ong, Diana M Veillon, James D Cotelingam, Rodney E Shackelford
Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29146547/a-gene-module-associated-with-dysregulated-tcr-signaling-pathways-in-cd4-t-cell-subsets-in-rheumatoid-arthritis
#15
Shuji Sumitomo, Yasuo Nagafuchi, Yumi Tsuchida, Haruka Tsuchiya, Mineto Ota, Kazuyoshi Ishigaki, Shinichiro Nakachi, Rika Kato, Keiichi Sakurai, Norio Hanata, Shoko Tateishi, Hiroko Kanda, Akari Suzuki, Yuta Kochi, Keishi Fujio, Kazuhiko Yamamoto
We analyzed the transcriptome of detailed CD4(+) T cell subsets including them after abatacept treatment, and examined the difference among CD4(+) T cell subsets and identified gene sets that are closely associated disease activity and abatacept treatment. Seven CD4(+) T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh and Treg) were sorted from PBMCs taken from 10 RA patients and 10 healthy controls, and three RA patients donated samples before and 6 months after abatacept treatment. Paired-end RNA sequencing was performed using HiSeq 2500...
November 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#16
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#17
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142309/hypercholesterolemia-enhances-t-cell-receptor-signaling-and-increases-the-regulatory-t-cell-population
#18
Reiner K W Mailer, Anton Gisterå, Konstantinos A Polyzos, Daniel F J Ketelhuth, Göran K Hansson
Hypercholesterolemia promotes the inflammation against lipoproteins in atherosclerosis. Development of atherosclerosis is affected by the balance between pro-inflammatory effector T cells and anti-inflammatory regulatory T (Treg) cells. However, phenotype and function of T cell subpopulations in hypercholesterolemia remain to be investigated. Here, we found that cholesterol-containing diet increased the expression of the Treg cell lineage-defining transcription factor FoxP3 among thymocytes and splenocytes...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142275/nf-%C3%AE%C2%BAb-protects-nkt-cells-from-tumor-necrosis-factor-receptor-1-induced-death
#19
Amrendra Kumar, Laura E Gordy, Jelena S Bezbradica, Aleksandar K Stanic, Timothy M Hill, Mark R Boothby, Luc Van Kaer, Sebastian Joyce
Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-xL-coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas...
November 15, 2017: Scientific Reports
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
#20
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
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