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https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#1
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29033130/tumor-and-microenvironment-evolution-during-immunotherapy-with-nivolumab
#2
Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter J Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy...
October 11, 2017: Cell
https://www.readbyqxmd.com/read/29028876/systematic-comparative-study-of-computational-methods-for-t-cell-receptor-sequencing-data-analysis
#3
Saira Afzal, Irene Gil-Farina, Richard Gabriel, Shahzad Ahmad, Christof von Kalle, Manfred Schmidt, Raffaele Fronza
High-throughput sequencing technologies have exposed the possibilities for the in-depth evaluation of T-cell receptor (TCR) repertoires. These studies are highly relevant to gain insights into human adaptive immunity and to decipher the composition and diversity of antigen receptors in physiological and disease conditions. The major objective of TCR sequencing data analysis is the identification of V, D and J gene segments, complementarity-determining region 3 (CDR3) sequence extraction and clonality analysis...
September 23, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29022222/t-cell-receptor-profiling-in-type-1-diabetes
#4
REVIEW
Laura M Jacobsen, Amanda Posgai, Howard R Seay, Michael J Haller, Todd M Brusko
PURPOSE OF REVIEW: The genetic susceptibility and dominant protection for type 1 diabetes (T1D) associated with human leukocyte antigen (HLA) haplotypes, along with minor risk variants, have long been thought to shape the T cell receptor (TCR) repertoire and eventual phenotype of autoreactive T cells that mediate β-cell destruction. While autoantibodies provide robust markers of disease progression, early studies tracking autoreactive T cells largely failed to achieve clinical utility...
October 11, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#5
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4(+) T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4(+) T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28986544/a-novel-mouse-model-of-inkt-cell-deficiency-generated-by-crispr-cas9-reveals-a-pathogenic-role-of-inkt-cells-in-metabolic-disease
#6
Yue Ren, Etsuko Sekine-Kondo, Risa Shibata, Megumi Kato-Itoh, Ayumi Umino, Ayaka Yanagida, Masashi Satoh, Komaki Inoue, Tomoyuki Yamaguchi, Keiichi Mochida, Susumu Nakae, Luc Van Kaer, Kazuya Iwabuchi, Hiromitsu Nakauchi, Hiroshi Watarai
iNKT cells play important roles in immune regulation by bridging the innate and acquired immune systems. The functions of iNKT cells have been investigated in mice lacking the Traj18 gene segment that were generated by traditional embryonic stem cell technology, but these animals contain a biased T cell receptor (TCR) repertoire that might affect immune responses. To circumvent this confounding factor, we have generated a new strain of iNKT cell-deficient mice by deleting the Traj18 locus using CRISPR/Cas9 technology, and these animals contain an unbiased TCR repertoire...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28977646/vdjdb-a-curated-database-of-t-cell-receptor-sequences-with-known-antigen-specificity
#7
Mikhail Shugay, Dmitriy V Bagaev, Ivan V Zvyagin, Renske M Vroomans, Jeremy Chase Crawford, Garry Dolton, Ekaterina A Komech, Anastasiya L Sycheva, Anna E Koneva, Evgeniy S Egorov, Alexey V Eliseev, Ewald Van Dyk, Pradyot Dash, Meriem Attaf, Cristina Rius, Kristin Ladell, James E McLaren, Katherine K Matthews, E Bridie Clemens, Daniel C Douek, Fabio Luciani, Debbie van Baarle, Katherine Kedzierska, Can Kesmir, Paul G Thomas, David A Price, Andrew K Sewell, Dmitriy M Chudakov
The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes...
September 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28975891/local-immune-response-in-cutaneous-basal-cell-carcinoma
#8
Silje Haukali Omland
BCC is an immunogenic tumor highlighted by the increased risk in immunosuppressed individuals and the frequent occurrence of tumor infiltrating lymphocytes (TILs) in the tumor surroundings. Immunotherapy is evolving as a promising treatment strategy for several cancer types where topical immunostimulators are among the possibilities for superficial BCC. The overall aim of this thesis is to characterize the immunologic response upon BCC as well as characterizing the surrounding tumor stroma. The aim was achieved by the use of a variety of laboratory techniques; immunohistochemistry, immunoflourescence, qRT-PCR and NGS...
October 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28975614/t-cell-receptor-alpha-variable-12-2-bias-in-the-immunodominant-response-to-yellow-fever-virus
#9
Amandine Bovay, Vincent Zoete, Garry Dolton, Anna M Bulek, David K Cole, Pierre J Rizkallah, Anna Fuller, Konrad Beck, Olivier Michielin, Daniel E Speiser, Andrew K Sewell, Silvia A Fuertes Marraco
The repertoire of human αβ T cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias towards a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8(+) T cell response to the highly effective YF-17D vaccine...
October 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28972091/cd8-t-cells-prevent-lethality-from-neonatal-murine-roseolovirus-infection
#10
Swapneel J Patel, Wayne M Yokoyama
A recently described mouse homolog of the human roseoloviruses, murine roseolovirus (MRV), causes loss of peripheral and thymic CD4(+) cells during neonatal infection of BALB/c mice. Despite significant disruptions to the normal adaptive immune response, infected BALB/c mice reproducibly recover from infection, consistent with prior studies on a related virus, mouse thymic virus. In this article, we show that, in contrast to published studies on mouse thymic virus, MRV appears to robustly infect neonatal C57BL/6 (B6) mice, causing severe depletion of thymocytes and peripheral T cells...
October 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28970488/single-cell-analysis-reveals-sexually-dimorphic-repertoires-of-interferon-%C3%AE-and-il-17a-producing-t-cells-in-salivary-glands-of-sj%C3%A3-gren-s-syndrome-mice
#11
Arun Wanchoo, Alexandria Voigt, Sukesh Sukumaran, Carol M Stewart, Indraneel Bhattacharya, Cuong Q Nguyen
The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjS(s)) C57BL/6...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28947567/4-1bb-agonist-focuses-cd8-tumor-infiltrating-t-cell-growth-into-a-distinct-repertoire-capable-of-tumor-recognition-in-pancreatic-cancer
#12
Donastas Sakellariou-Thompson, Marie-Andrée Forget, Caitlin Creasy, Vincent Bernard, Li Zhao, Young Uk Kim, Mark W Hurd, Naohiro Uraoka, Edwin R Parra, Ya'an Kang, Christopher A Bristow, Jaime Rodriguez-Canales, Jason B Fleming, Gauri R Varadhachary, Milind Javle, Michael J Overman, Hector A Alvarez, Timothy P Heffernan, Jianhua Zhang, Patrick Hwu, Anirban Maitra, Cara Haymaker, Chantale Bernatchez
PURPOSE: Survival for pancreatic ductal adenocarcinoma (PDAC) patients is extremely poor and improved therapies are urgently needed. Tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) has shown great promise in other tumor types, such as metastatic melanoma where overall response rates of 50% have been seen. Given this success and the evidence showing that T-cell presence positively correlates with overall survival in PDAC, we sought to enrich for CD8+ TIL capable of autologous tumor recognition...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28945243/germline-bias-dictates-cross-serotype-reactivity-in-a-common-dengue-virus-specific-cd8-t-cell-response
#13
Abigail Culshaw, Kristin Ladell, Stephanie Gras, James E McLaren, Kelly L Miners, Carine Farenc, Heleen van den Heuvel, Emma Gostick, Wanwisa Dejnirattisai, Apirath Wangteeraprasert, Thaneeya Duangchinda, Pojchong Chotiyarnwong, Wannee Limpitikul, Sirijitt Vasanawathana, Prida Malasit, Tao Dong, Jamie Rossjohn, Juthathip Mongkolsapaya, David A Price, Gavin R Screaton
Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4...
November 2017: Nature Immunology
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#14
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28928269/perturbed-cd8-t-cell-immunity-across-universal-influenza-epitopes-in-the-elderly
#15
Thi H O Nguyen, Sneha Sant, Nicola L Bird, Emma J Grant, E Bridie Clemens, Marios Koutsakos, Sophie A Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska
Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8(+) T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8(+) T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8(+) T cells...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28924003/learning-the-high-dimensional-immunogenomic-features-that-predict-public-and-private-antibody-repertoires
#16
Victor Greiff, Cédric R Weber, Johannes Palme, Ulrich Bodenhofer, Enkelejda Miho, Ulrike Menzel, Sai T Reddy
Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone-specific immunogenomic differences concentrated in CDR3's N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28900149/assessment-of-t-cell-receptor-repertoire-and-clonal-expansion-in-peripheral-t-cell-lymphoma-using-rna-seq-data
#17
Qiang Gong, Chao Wang, Weiwei Zhang, Javeed Iqbal, Yang Hu, Timothy C Greiner, Adam Cornish, Jo-Heon Kim, Raul Rabadan, Francesco Abate, Xin Wang, Giorgio G Inghirami, Timothy W McKeithan, Wing C Chan
T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891256/composition-and-variation-analysis-of-the-t-cell-receptor-%C3%AE-chain-complementarity-determining-region-3-repertoire-in-neonatal-sepsis
#18
J Sun, B Sun, Y Gao, F He, L Yang, M Wang, W Zhou
T cell receptor (TCR) diversity is clearly related to protection from infection. However, the characteristics of TCR diversity in neonates are not clear. In this study, we investigated the TCR diversity of neonates with sepsis. Twenty neonates with severe sepsis and eight matched neonates without infection were enrolled in the study. For the neonates with sepsis, EDTA-anticoagulated blood was collected on day 1 after the diagnosis of sepsis and on day 7 of treatment. For the neonates without infection, blood was collected one time...
November 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28888033/modulation-of-%C3%AE-%C3%AE-t-cell-activation-by-neutrophil-elastase
#19
Nadia Yasmín Towstyka, Carolina Maiumi Shiromizu, Irene Keitelman, Florencia Sabbione, Gabriela Verónica Salamone, Jorge Raúl Geffner, Analía Silvina Trevani, Carolina Cristina Jancic
γδ T cells are non-conventional, innate-like T cells, characterized by a restricted TCR repertoire. They participate in protective immunity response against extracellular and intracellular pathogens, tumor surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance, and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of IFN-γ and TNF-α induced by anti-CD3 antibodies were potentiated by neutrophils...
September 9, 2017: Immunology
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#20
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
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