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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/28423320/sequence-and-structural-analyses-reveal-distinct-and-highly-diverse-human-cd8-tcr-repertoires-to-immunodominant-viral-antigens
#2
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/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#3
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/28416603/high-throughput-immunogenetics-for-clinical-and-research-applications-in-immunohematology-potential-and-challenges
#4
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
#5
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/28409183/combination-of-il-10-and-il-2-induces-oligoclonal-human-cd4-t-cell-expansion-during-xenogeneic-and-allogeneic-gvhd-in-humanized-mice
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28377772/treatment-of-pediatric-acute-graft-versus-host-disease-lessons-from-primary-immunodeficiency
#9
REVIEW
Aisling M Flinn, Andrew R Gennery
Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28377595/gvl-effects-in-t-prolymphocytic-leukemia-evidence-from-mrd-kinetics-and-tcr-repertoire-analyses
#10
L Sellner, M Brüggemann, M Schlitt, H Knecht, D Herrmann, T Reigl, A Krejci, V Bystry, N Darzentas, M Rieger, S Dietrich, T Luft, A D Ho, M Kneba, P Dreger
No abstract text is available yet for this article.
April 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28369043/generation-of-mature-t-cells-from-human-hematopoietic-stem-and-progenitor-cells-in-artificial-thymic-organoids
#11
Christopher S Seet, Chongbin He, Michael T Bethune, Suwen Li, Brent Chick, Eric H Gschweng, Yuhua Zhu, Kenneth Kim, Donald B Kohn, David Baltimore, Gay M Crooks, Amélie Montel-Hagen
Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3(+)TCR-αβ(+) single-positive CD8(+) or CD4(+) cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs...
May 2017: Nature Methods
https://www.readbyqxmd.com/read/28369038/immunosequencing-identifies-signatures-of-cytomegalovirus-exposure-history-and-hla-mediated-effects-on-the-t-cell-repertoire
#12
Ryan O Emerson, William S DeWitt, Marissa Vignali, Jenna Gravley, Joyce K Hu, Edward J Osborne, Cindy Desmarais, Mark Klinger, Christopher S Carlson, John A Hansen, Mark Rieder, Harlan S Robins
An individual's T cell repertoire dynamically encodes their pathogen exposure history. To determine whether pathogen exposure signatures can be identified by documenting public T cell receptors (TCRs), we profiled the T cell repertoire of 666 subjects with known cytomegalovirus (CMV) serostatus by immunosequencing. We developed a statistical classification framework that could diagnose CMV status from the resulting catalog of TCRβ sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects...
May 2017: Nature Genetics
https://www.readbyqxmd.com/read/28358435/clinical-significance-of-t-cell-clonality-and-expression-levels-of-immune-related-genes-in-endometrial-cancer
#13
Yuji Ikeda, Kazuma Kiyotani, Poh Yin Yew, Sho Sato, Yuichi Imai, Rui Yamaguchi, Satoru Miyano, Keiichi Fujiwara, Kosei Hasegawa, Yusuke Nakamura
Immune microenvironment characterized by T cell clonality as well as expression signatures of immune-related genes in endometrial cancer tissues may play significant roles in clinical outcome of patients. We aimed to investigate the clinical significance of immune-related gene expression and TCR repertoire in endometrial cancer. Using total RNAs extracted from 32 endometrioid endometrial cancer cases, we performed quantitative real-time PCR to measure mRNA expression levels of immune-related genes including TRB, CD8, GZMA, HLA-A, CD11c and PD-L1...
March 29, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#14
Bergithe E Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R Holdsworth, Christopher N Hahn, Andreas W Schreiber, Hamish S Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs...
March 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28300170/cd8-t-cells-specific-for-the-islet-autoantigen-igrp-are-restricted-in-their-t-cell-receptor-chain-usage
#15
Yannick F Fuchs, Anne Eugster, Sevina Dietz, Christian Sebelefsky, Denise Kühn, Carmen Wilhelm, Annett Lindner, Anita Gavrisan, Jan Knoop, Andreas Dahl, Anette-G Ziegler, Ezio Bonifacio
CD8(+) T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8(+) T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8(+) T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer(+) CD8(+) T cells representing 48 clonotypes were obtained...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290464/blocking-the-recruitment-of-naive-cd4-t-cells-reverses-immunosuppression-in-breast-cancer
#16
Shicheng Su, Jianyou Liao, Jiang Liu, Di Huang, Chonghua He, Fei Chen, LinBing Yang, Wei Wu, Jianing Chen, Ling Lin, Yunjie Zeng, Nengtai Ouyang, Xiuying Cui, Herui Yao, Fengxi Su, Jian-Dong Huang, Judy Lieberman, Qiang Liu, Erwei Song
The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4(+) T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4(+) T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients...
April 2017: Cell Research
https://www.readbyqxmd.com/read/28284194/clonocalc-and-clonoplot-immune-repertoire-analysis-from-raw-files-to-publication-figures-with-graphical-user-interface
#17
Anke Fähnrich, Moritz Krebbel, Normann Decker, Martin Leucker, Felix D Lange, Kathrin Kalies, Steffen Möller
BACKGROUND: Next generation sequencing (NGS) technologies enable studies and analyses of the diversity of both T and B cell receptors (TCR and BCR) in human and animal systems to elucidate immune functions in health and disease. Over the last few years, several algorithms and tools have been developed to support respective analyses of raw sequencing data of the immune repertoire. These tools focus on distinct aspects of the data processing and require a strong bioinformatics background...
March 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28264997/generation-of-peptides-that-promote-positive-selection-in-the-thymus
#18
REVIEW
Kensuke Takada, Kenta Kondo, Yousuke Takahama
To establish an immunocompetent TCR repertoire that is useful yet harmless to the body, a de novo thymocyte repertoire generated through the rearrangement of genes that encode TCR is shaped in the thymus through positive and negative selection. The affinity between TCRs and self-peptides associated with MHC molecules determines the fate of developing thymocytes. Low-affinity TCR engagement with self-peptide-MHC complexes mediates positive selection, a process that primarily occurs in the thymic cortex. Massive efforts exerted by many laboratories have led to the characterization of peptides that can induce positive selection...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28264971/the-lower-limit-of-regulatory-cd4-foxp3-tcr%C3%AE-repertoire-diversity-required-to-control-autoimmunity
#19
Aixin Yu, Michael J Dee, Dennis Adeegbe, Connor J Dwyer, Norman H Altman, Thomas R Malek
The TCR repertoire of regulatory T cells (Tregs) is highly diverse. The relevance of this diversity to maintain self-tolerance remains unknown. We established a model where the TCR repertoire of normal polyclonal Tregs was limited by serial transfers into IL-2Rβ(-/-) mice, which lack functional Tregs. After a primary transfer, the donor Treg TCR repertoire was substantially narrowed, yet the recipients remained autoimmune-free. Importantly, upon purification and transfer of donor-derived Tregs from an individual primary recipient into neonatal IL-2Rβ(-/-) mice, the secondary recipients developed autoimmunity...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28261218/the-t-cell-response-to-the-contact-sensitizer-paraphenylenediamine-is-characterized-by-a-polyclonal-diverse-repertoire-of-antigen-specific-receptors
#20
Theres Oakes, Amy Lee Popple, Jason Williams, Katharine Best, James M Heather, Mazlina Ismail, Gavin Maxwell, Nichola Gellatly, Rebecca J Dearman, Ian Kimber, Benny Chain
Paraphenylenediamine (PPD) is a common component of hair dyes and black henna tattoos and can cause skin sensitization and allergic contact dermatitis (ACD). The cutaneous inflammatory reaction associated with ACD is driven by both CD4+ and CD8+ T cells. However, the characteristics of such responses with respect to clonal breadth and magnitude are poorly defined. In this study, we have characterized the in vitro recall response of peripheral blood T cells prepared from PPD-allergic individuals to a PPD-human serum albumin (HSA) conjugate (PPD-HSA)...
2017: Frontiers in Immunology
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