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https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#1
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28535950/aging-related-changes-in-human-t-cell-repertoire-over-20years-delineated-by-deep-sequencing-of-peripheral-t-cell-receptors
#2
Kengo Yoshida, John B Cologne, Kismet Cordova, Munechika Misumi, Mika Yamaoka, Seishi Kyoizumi, Tomonori Hayashi, Harlan Robins, Yoichiro Kusunoki
Recent deep sequencing studies on T-cell receptor (TCR) repertoire have provided robust data to characterize diversity of T-cell immune responsiveness to a wide variety of peptide antigens, including viral and tumor antigens. The human TCR repertoire declines with age, but this decline has not been fully investigated longitudinally in individuals. Using a deep sequencing approach, we analyzed TCRβ repertoires longitudinally over approximately 20years, with ages ranging from 23 to 50years at the start (23 to 65years overall), in peripheral-blood CD4 and CD8 T-cell populations that were collected and cryopreserved 3 times at intervals of approximately 10years from each of 6 healthy adults (3 men and 3 women)...
May 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28508570/a-new-transcript-in-the-tcrb-locus-unveils-the-human-ortholog-of-the-mouse-pre-d%C3%A3-1-promoter
#3
Bernard Lethé, Sylvia Snauwaert, Orian Bricard, David Schröder, Tiphanie Gomard, Gérald Hames, Catherine Muller, Christophe Lurquin, Emilie Gauthy, Ahmed Essaghir, Bart Vandekerckhove, Pierre G Coulie
INTRODUCTION: While most transcripts arising from the human T Cell Receptor locus reflect fully rearranged genes, several germline transcripts have been identified. We describe a new germline transcript arising from the human TCRB locus. METHODS: cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript. RESULTS: The new germline transcript encoded by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1 (X1), spliced with the first exon of gene segments Cß1 or Cß2...
May 15, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28320875/gata3-abundance-is-a-critical-determinant-of-t-cell-receptor-beta-allelic-exclusion
#4
Chia-Jui Ku, JoAnn M Sekiguchi, Bharat Panwar, Yuanfang Guan, Satoru Takahashi, Keigyou Yoh, Ivan Maillard, Tomonori Hosoya, James Douglas Engel
Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild type mammals, approximately 60% of cells have recombined the DNA of one Tcrb V-to-DJ-joined allele in a functional configuration, while the second allele has only recombined the DJ sequences; the other 40% of the cells have recombined the V- to the DJ segments on both alleles, with only one of the two predicting a functional TCRβ protein...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28316595/effects-of-copper-addition-on-copper-resistance-antibiotic-resistance-genes-and-intl1-during-swine-manure-composting
#5
Yanan Yin, Jie Gu, Xiaojuan Wang, Wen Song, Kaiyu Zhang, Wei Sun, Xin Zhang, Yajun Zhang, Haichao Li
Copper is one of the most abundant heavy metals present in swine manure. In this study, a laboratory-scale aerobic composting system was amended with Cu at three levels (0, 200, and 2000 mg kg(-1), i.e., control, Cu200, and Cu2000 treatments, respectively) to determine its effect on the fate of copper resistance genes [copper resistance genes (CRGs): pcoA, cusA, copA, and tcrB], antibiotic resistance genes [antibiotic resistance genes (ARGs): erm(A) and erm(B)], and intl1. The results showed that the absolute abundances of pcoA, tcrB, erm(A), erm(B), and intl1 were reduced, whereas those of copA and cusA increased after swine manure composting...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28244489/chromosome-choice-for-initiation-of-v-d-j-recombination-is-not-governed-by-genomic-imprinting
#6
Claudia Gebert, Lauren Correia, Zhenhu Li, Howard T Petrie, Paul E Love, Karl Pfeifer
V-(D)-J recombination generates the antigen receptor diversity necessary for immune cell function, while allelic exclusion ensures that each cell expresses a single antigen receptor. V-(D)-J recombination of the Ig, Tcrb, Tcrg and Tcrd antigen receptor genes is ordered and sequential so that only one allele generates a productive rearrangement. The mechanism controlling sequential rearrangement of antigen receptor genes, in particular how only one allele is selected to initiate recombination while at least temporarily leaving the other intact, remains unresolved...
May 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28212502/a-new-mechanism-shapes-the-na%C3%A3-ve-cd8-t-cell-repertoire-the-selection-for-full-diversity
#7
Pedro Gonçalves, Marco Ferrarini, Carmen Molina-Paris, Grant Lythe, Florence Vasseur, Annik Lim, Benedita Rocha, Orly Azogui
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clonal sizes...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28150718/distinct-requirement-of-runx-complexes-for-tcr%C3%AE-enhancer-activation-at-distinct-developmental-stages
#8
Wooseok Seo, Sawako Muroi, Kaori Akiyama, Ichiro Taniuchi
A TCRβ enhancer, known as the Eβ enhancer, plays a critical role in V(D)J recombination and transcription of the Tcrb gene. However, the coordinated action of trans-acting factors in the activation of Eβ during T cell development remains uncharacterized. Here, we characterized the roles of Runx complexes in the regulation of the Eβ function. A single mutation at one of the two Runx binding motifs within the Eβ severely impaired Tcrb activation at the initiation phase in immature thymocytes. However, TCRβ expression level in mature thymocytes that developed under such a single Runx site mutation was similar to that of the control...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137913/chromatin-domain-organization-of-the-tcrb-locus-and-its-perturbation-by-ectopic-ctcf-binding
#9
Pratishtha Rawat, Manisha Jalan, Ananya Sadhu, Abhilasha Kanaujia, Madhulika Srivastava
CTCF-mediated chromatin interactions influence organization and function of mammalian genome in diverse ways. We analyzed the interactions among CTCF binding sites (CBS) at the murine TCRb locus to discern the role of CTCF-mediated interactions in the regulation of transcription and VDJ recombination. Chromosome conformation capture analysis revealed thymocyte-specific long-range intrachromosomal interactions among various CBS across the locus that were relevant for defining the limit of the enhancer Eb-regulated recombination center (RC) and for facilitating the spatial proximity of TCRb variable (V) gene segments to the RC...
May 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#10
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#11
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27880974/deep-sequencing-of-the-tcr-%C3%AE-repertoire-of-human-forkhead-box-protein-3-foxp3-and-foxp3-t-cells-suggests-that-they-are-completely-distinct-and-non-overlapping
#12
A Golding, S Darko, W H Wylie, D C Douek, E M Shevach
Maintenance of peripheral tolerance requires a balance between autoreactive conventional T cells (Tconv ) and thymically derived forkhead box protein 3 (FoxP3)(+) regulatory T cells (tTregs ). Considerable controversy exists regarding the similarities/differences in T cell receptor (TCR) repertoires expressed by Tconv and tTregs . We generated highly purified populations of human adult and cord blood Tconv and tTregs based on the differential expression of CD25 and CD127. The purity of the sorted populations was validated by intracellular staining for FoxP3 and Helios...
April 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27590759/effect-of-coenzyme-q10-on-proteomic-profile-of-rat-brain-amygdala-during-acute-metabolic-stress
#13
N V Kirbaeva, N E Sharanova, V M Zhminchenko, I Yu Toropygin, E V Koplik, S S Pertsov, A V Vasil'ev
Differences in the proteomic profiles of the brain amygdala in rats with different prognostic resistance to stress were found on the model of metabolic stress. Differential expression of tropomodulin-2, GTP-binding protein SAR1, peroxiredoxin-2, calcineurin B homologous protein 1, Ras-related protein Rab-14, glutathione S-transferase omega-1, Tcrb protein, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (mitochondrial) was shown to depend on the behavioral pattern of animals and stage of the study...
August 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27542204/nucks1-synergizes-with-trp53-to-promote-radiation-lymphomagenesis-in-mice
#14
Yangbo Yue, Stanley G Leung, Yueyong Liu, Yurong Huang, Kirsten Grundt, Anne-Carine Østvold, Kuang-Yu Jen, David Schild, Jian-Hua Mao, Claudia Wiese
NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27499053/streptococcus-agalactiae-from-pregnant-women-antibiotic-and-heavy-metal-resistance-mechanisms-and-molecular-typing
#15
B Rojo-Bezares, J M Azcona-Gutiérrez, C Martin, M S Jareño, C Torres, Y Sáenz
We investigated the antibiotic and heavy-metal resistance mechanisms, virulence genes and clonal relationships of macrolide- and/or lincosamide-resistant (M+/-LR) Streptococcus agalactiae (group B Streptococcus, GBS) isolates from pregnant women in La Rioja in Northern Spain, a region with a significant immigrant population. In total 375 GBS isolates were recovered during 2011. About three-quarters of isolates were from European nationals and the remainder distributed among 23 other nationalities. Seventy-five (20%) were classified as M+/-LR strains and 28 (37%) of these were resistant to ⩾3 classes of antibiotics...
November 2016: Epidemiology and Infection
https://www.readbyqxmd.com/read/27471234/t-cells-from-hemophilia-a-subjects-recognize-the-same-hla-restricted-fviii-epitope-with-a-narrow-tcr-repertoire
#16
Ruth A Ettinger, Pedro Paz, Eddie A James, Devi Gunasekera, Fred Aswad, Arthur R Thompson, Dana C Matthews, Kathleen P Pratt
Factor VIII (FVIII)-neutralizing antibodies ("inhibitors") are a serious problem in hemophilia A (HA). The aim of this study was to characterize HLA-restricted T-cell responses from a severe HA subject with a persistent inhibitor and from 2 previously studied mild HA inhibitor subjects. Major histocompatibility complex II tetramers corresponding to both of the severe HA subject's HLA-DRA-DRB1 alleles were loaded with peptides spanning FVIII-A2, C1, and C2 domains. Interestingly, only 1 epitope was identified, in peptide FVIII2194-2213, and it was identical to the HLA-DRA*01-DRB1*01:01-restricted epitope recognized by the mild HA subjects...
October 20, 2016: Blood
https://www.readbyqxmd.com/read/27465739/characterization-of-the-t-cell-receptor-beta-chain-repertoire-in-tumor-infiltrating-lymphocytes
#17
Katsumi Nakanishi, Yoji Kukita, Hidenobu Segawa, Norimitsu Inoue, Masayuki Ohue, Kikuya Kato
Tumor-infiltrating lymphocytes (TILs) are direct effectors of tumor immunity, and their characterization is important for further development of immunotherapy. Recent advances in high-throughput sequencing technologies have enabled a comprehensive analysis of T-cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, which may provide information of therapeutic importance. We developed a high-fidelity target sequencing method with the ability for absolute quantitation, and performed large-scale sequencing of TCR beta chain (TCRB) CDR3 regions in TILs and peripheral blood lymphocytes (PBLs)...
September 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27452728/immune-dna-signature-of-t-cell-infiltration-in-breast-tumor-exomes
#18
Eric Levy, Rachel Marty, Valentina Gárate Calderón, Brian Woo, Michelle Dow, Ricardo Armisen, Hannah Carter, Olivier Harismendy
Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27439714/identification-of-multi-loci-hubs-from-4c-seq-demonstrates-the-functional-importance-of-simultaneous-interactions
#19
Tingting Jiang, Ramya Raviram, Valentina Snetkova, Pedro P Rocha, Charlotte Proudhon, Sana Badri, Richard Bonneau, Jane A Skok, Yuval Kluger
Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these...
October 14, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27370973/an-oral-chitosan-dna-vaccine-against-nodavirus-improves-transcription-of-cell-mediated-cytotoxicity-and-interferon-genes-in-the-european-sea-bass-juveniles-gut-and-survival-upon-infection
#20
Yulema Valero, Elham Awad, Francesco Buonocore, Marta Arizcun, M Ángeles Esteban, José Meseguer, Elena Chaves-Pozo, Alberto Cuesta
Vaccines for fish need to be improved for the aquaculture sector, with DNA vaccines and the oral administration route providing the most promising improvements. In this study, we have created an oral chitosan-encapsulated DNA vaccine (CP-pNNV) for the nodavirus (NNV) in order to protect the very susceptible European sea bass (Dicentrarchus labrax). Our data show that the oral CP-pNNV vaccine failed to induce serum circulating or neutralizing specific antibodies (immunoglobulin M) or to up-regulate their gene expression in the posterior gut...
December 2016: Developmental and Comparative Immunology
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