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https://www.readbyqxmd.com/read/28429709/t-follicular-helper-and-t-follicular-regulatory-cells-have-different-tcr-specificity
#1
Ana Raquel Maceiras, Silvia Cristina Paiva Almeida, Encarnita Mariotti-Ferrandiz, Wahiba Chaara, Fadi Jebbawi, Adrien Six, Shohei Hori, David Klatzmann, Jose Faro, Luis Graca
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428787/a-possible-role-for-idiotype-anti-idiotype-b-t-cell-interactions-in-maintaining-immune-memory
#2
Victor I Seledtsov, Galina V Seledtsova
Variable regions of both B-cell receptors (BCRs) and T-cell receptors (TCRs) are completely formed in the postnatal period, and, consequently, no innate immune tolerance against these structures exists in adulthood. Indeed, antibodies (Abs) specific to TCRs have been found in both animals and humans. These facts clearly indicate the existence of B cells able to directly interact with T cells through binding of BCRs to TCRs without implicating major histocompatibility complex molecules. A novel paradigm is proposed in that the immune memory is based on idiotype/anti-idiotype interactions occurring between BCRs and TCRs following clearance of the antigen that elicited immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#3
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28426533/hiv-dna-content-in-different-cd4-t-cell-subsets-correlates-with-cd4-cd8-ratio-or-length-of-efficient-treatment
#4
Lara Gibellini, Simone Pecorini, Sara de Biasi, Elena Bianchini, Margherita Digaetano, Marcello Pinti, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Cristina Mussini, Andrea Cossarizza, Milena Nasi
OBJECTIVES: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy (cART), our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4+ T cell subsets. METHODS: We enrolled 32 HIV+ patients successfully treated for > 2 years, with a CD4+ T cell count > 500 cells/μL and plasma viremia undetectable from at least one year...
April 19, 2017: AIDS
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#5
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423320/sequence-and-structural-analyses-reveal-distinct-and-highly-diverse-human-cd8-tcr-repertoires-to-immunodominant-viral-antigens
#6
Guobing Chen, Xinbo Yang, Annette Ko, Xiaoping Sun, Mingming Gao, Yongqing Zhang, Alvin Shi, Roy A Mariuzza, Nan-Ping Weng
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8(+) TCR repertoires for two dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#7
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#8
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418392/gene-enhancer-variants-reveal-diverse-tcr-mediated-differentiation
#9
Michael P Gallagher, Leslie J Berg
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28416722/correction-prevention-of-v%C3%AE-9v%C3%AE-2-t-cell-activation-by-a-v%C3%AE-9v%C3%AE-2-tcr-nanobody
#10
Renée C G de Bruin, Anita G M Stam, Anna Vangone, Paul M P van Bergen En Henegouwen, Henk M W Verheul, Zsolt Sebestyén, Jürgen Kuball, Alexandre M J J Bonvin, Tanja D de Gruijl, Hans J van der Vliet
No abstract text is available yet for this article.
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416603/high-throughput-immunogenetics-for-clinical-and-research-applications-in-immunohematology-potential-and-challenges
#11
Anton W Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J M van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A Macintyre, Michael Hummel, Christiane Pott, Patricia J T A Groenen, Kostas Stamatopoulos
Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416602/antigen-receptor-galaxy-a-user-friendly-web-based-tool-for-analysis-and-visualization-of-t-and-b-cell-receptor-repertoire-data
#12
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Andrew P Stubbs, Mirjam van der Burg
Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of four parts: the demultiplex tool, the international ImMunoGeneTics information system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they allow the analysis of all different aspects of the immune repertoire. All pipelines can be run independently or combined, depending on the available data and the question of interest...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28415650/a-highly-conserved-redox-active-mx-2-cwx-6-r-motif-regulates-zap70-stability-and-activity
#13
Christoph Thurm, Mateusz P Poltorak, Elisa Reimer, Melanie M Brinkmann, Lars Leichert, Burkhart Schraven, Luca Simeoni
ζ-associated protein of 70 kDa (Zap70) is crucial for T-cell receptor (TCR) signaling. Loss of Zap70 in both humans and mice results in severe immunodeficiency. On the other hand, the expression of Zap70 in B-cell malignancies correlates with the severity of the disease. Because of its role in immune-related disorders, Zap70 has become a therapeutic target for the treatment of human diseases. It is well-established that the activity/expression of Zap70 is regulated by post-translational modifications of crucial amino acids including the phosphorylation of tyrosines and the ubiquitination of lysines...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414558/th17-inducing-conditions-lead-to-in-vitro-activation-of-both-th17-and-th1-responses-in-behcet-s-disease
#14
Rabia Deniz, Aysın Tulunay-Virlan, Filiz Ture Ozdemir, Ali Ugur Unal, Gulsen Ozen, Fatma Alibaz-Oner, Imren Aydin-Tatli, Gonca Mumcu, Tulin Ergun, Haner Direskeneli
OBJECTIVES: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet's disease (BD). METHODS: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1β, and IL-23) for 6 days...
April 17, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28413552/trigeminocardiac-reflex-preceding-development-of-postoperative-superior-orbital-fissure-syndrome
#15
Rudrashish Haldar, Prakhar Gyanesh, Arun Srivastava, Guru Prasad Bettaswamy
The superior orbital fissure syndrome (SOFS) is a rare condition presenting as painful unilateral opthalmoplegia, ptosis, pupillary dilatation and anesthesia of the upper eyelid and forehead. It has been described after facial trauma. Other etiologies include infections, tumors or spontaneous hemorrhages in the retro-orbital space. Occurrence of SOFS after surgery in the skull base has not been described before. We recently encountered a case where a young female developed SOFS following surgery for cerebrospinal fluid (CSF) rhinorrhea...
January 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/28412245/cxcr5-cd8-t-cells-infiltrate-the-colorectal-tumors-and-nearby-lymph-nodes-and-are-associated-with-enhanced-igg-response-in-b-cells
#16
Junjie Xing, Chenxin Zhang, Xiaohong Yang, Shaoxuan Wang, Zhongchuan Wang, Xu Li, Enda Yu
Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5(+)CD8(+) T cells present more potent proinflammatory function than CXCR5(-)CD8(+) T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5(+)CD8(+) T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5(+)CD8(+) T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#17
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28409183/combination-of-il-10-and-il-2-induces-oligoclonal-human-cd4-t-cell-expansion-during-xenogeneic-and-allogeneic-gvhd-in-humanized-mice
#18
Sojan Abraham, Hua Guo, Jang-Gi Choi, Chunting Ye, Midhun Ben Thomas, Nora Ortega, Alok Dwivedi, N Manjunath, Guohua Yi, Premlata Shankar
IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28405508/antigen-receptor-redirected-t-cells-derived-from-hematopoietic-precursor-cells-lack-expression-of-the-endogenous-tcr-cd3-receptor-and-exhibit-specific-antitumor-capacities
#19
Yasmine Van Caeneghem, Stijn De Munter, Paola Tieppo, Glenn Goetgeluk, Karin Weening, Greet Verstichel, Sarah Bonte, Tom Taghon, Georges Leclercq, Tessa Kerre, Reno Debets, David Vermijlen, Hinrich Abken, Bart Vandekerckhove
Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells derived from healthy allogeneic donors may have several advantages; however, the expected occurrence of graft versus host disease (GvHD) as a consequence of the diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells compromises this approach...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400082/immune-dysregulation-in-immunodeficiency-disorders-the-role-of-t-cell-receptor-sequencing
#20
REVIEW
Gabriel K Wong, James M Heather, Sara Barmettler, Mark Cobbold
Immune dysregulation is a prominent feature of primary immunodeficiency disorders, which commonly manifested as autoimmunity, cytopenias and inflammatory bowel disease. In partial T-cell immunodeficiency disorders, it has been proposed that the imbalance between effector and regulatory T-cells drives the breakdown of peripheral tolerance. While there is no robust test for immune dysregulation, the T-cell receptor repertoire is used as a surrogate marker, and has been shown to be perturbed in a number of immunodeficiency disorders featuring immune dysregulation including Omenn's Syndrome, Wiskott-Aldrich Syndrome, and common variable immunodeficiency...
April 8, 2017: Journal of Autoimmunity
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