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https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#1
Fei Teng, Krysta M Felix, C Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A Raslan, Hsin-Jung Joyce Wu
BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28798410/a-novel-signature-for-stratifying-the-molecular-heterogeneity-of-the-tissue-infiltrating-t-cell-receptor-repertoire-reflects-gastric-cancer-prognosis
#2
Manchao Kuang, Jieyao Cheng, Chengli Zhang, Lin Feng, Xue Xu, Yajing Zhang, Ming Zu, Jianfang Cui, Hang Yu, Kaitai Zhang, Aiming Yang, Shujun Cheng
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#3
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28783686/the-checkpoint-for-agonist-selection-precedes-conventional-selection-in-human-thymus
#4
Greet Verstichel, David Vermijlen, Liesbet Martens, Glenn Goetgeluk, Margreet Brouwer, Nicolas Thiault, Yasmine Van Caeneghem, Stijn De Munter, Karin Weening, Sarah Bonte, Georges Leclercq, Tom Taghon, Tessa Kerre, Yvan Saeys, Jo Van Dorpe, Hilde Cheroutre, Bart Vandekerckhove
The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist-selected lineages also relies on strong TCR signaling. How thymocytes discriminate between these opposite outcomes remains elusive. Here, we identified a human agonist-selected PD-1(+) CD8αα(+) subset of mature CD8αβ(+) T cells that displays an effector phenotype associated with agonist selection. TCR stimulation of immature post-β-selection thymocyte blasts specifically gives rise to this innate subset and fixes early T cell receptor alpha variable (TRAV) and T cell receptor alpha joining (TRAJ) rearrangements in the TCR repertoire...
February 24, 2017: Science Immunology
https://www.readbyqxmd.com/read/28775213/lactobacillus-reuteri-induces-gut-intraepithelial-cd4-cd8%C3%AE-%C3%AE-t-cells
#5
Luisa Cervantes-Barragan, Jiani N Chai, Ma Diarey Tianero, Blanda DiLuccia, Philip P Ahern, Joseph Merriman, Victor S Cortez, Michael G Caparon, Mohamed S Donia, Susan Gilfillan, Marina Cella, Jeffrey I Gordon, Chyi-Song Hsieh, Marco Colonna
The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28771750/comprehensive-t-cell-immunophenotyping-and-next-generation-sequencing-from-hpv-positive-and-negative-head-and-neck-squamous-cell-carcinomas
#6
Kate Poropatich, Joel Fontanarosa, Suchitra Swaminathan, Dave Dittmann, Siqi Chen, Sandeep Samant, Bin Zhang
The success of PD-1 inhibition in achieving a clinical response in a subset of HNSCC patients emphasizes the need to better understand the immunobiology of head and neck squamous cell carcinomas (HNSCC). Immunophenotyping was performed on 30 patients with HNSCC (16 HPV-positive, 14 HPV-negative) from matched tissue from the primary tumor site, locally metastatic cervical lymph nodes (LN), uninvolved local cervical LN and peripheral blood. CD4(+) and CD8(+) T cell lymphocytes obtained from tissue were analyzed for expression levels of inhibitory receptors PD-1, TIM-3 and CTLA-4...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28762987/autoreactive-t-cells-in-type-1-diabetes
#7
REVIEW
Alberto Pugliese
Type 1 diabetes (T1D) is a chronic autoimmune disease that causes severe loss of pancreatic β cells. Autoreactive T cells are key mediators of β cell destruction. Studies of organ donors with T1D that have examined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a broad repertoire of target antigens and T cell receptor (TCR) usage, with initial evidence of public TCR sequences that are shared by individuals with T1D. Neoepitopes derived from post-translational modifications of native antigens are emerging as novel targets that are more likely to evade self-tolerance...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28746867/tcr-signal-quality-modulates-fate-decisions-of-single-cd4-t-cells-in-a-probabilistic-manner
#8
Yi-Li Cho, Michael Flossdorf, Lorenz Kretschmer, Thomas Höfer, Dirk H Busch, Veit R Buchholz
To what extent the lineage decisions of activated CD4(+) T cells are determined by the quality of T cell receptor (TCR) ligation is incompletely understood. Here, we show that individual T cells expressing identical TCRs take highly variable fate decisions despite binding the same ligand. We identify a mathematical model that correctly captures this probabilistic behavior and allows one to formalize changes in TCR signal quality-due to cognate versus altered peptide ligation-as changes of lineage-specific proliferation and differentiation rates...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#9
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736203/oral-administration-of-visceral-adipose-tissue-antigens-ameliorates-metabolic-disorders-in-mice-and-elevates-visceral-adipose-tissue-resident-cd4-cd25-foxp3-regulatory-t-cells
#10
Xiangyu Chen, Dali Zhang, Xiaoling Chen, Gang Meng, Qian Zheng, Wenli Mai, Yuzhang Wu, Lilin Ye, Li Wang
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4(+)Foxp3(+) Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders...
July 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28733471/helicobacter-species-are-potent-drivers-of-colonic-t-cell-responses-in-homeostasis-and-inflammation
#11
Jiani N Chai, Yangqing Peng, Sunaina Rengarajan, Benjamin D Solomon, Teresa L Ai, Zeli Shen, Justin S A Perry, Kathryn A Knoop, Takeshi Tanoue, Seiko Narushima, Kenya Honda, Charles O Elson, Rodney D Newberry, Thaddeus S Stappenbeck, Andrew L Kau, Daniel A Peterson, James G Fox, Chyi-Song Hsieh
Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cell responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg cell responses during homeostasis and Teff cell responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733428/tcr-repertoire-intratumor-heterogeneity-in-localized-lung-adenocarcinomas-an-association-with-predicted-neoantigen-heterogeneity-and-postsurgical-recurrence
#12
Alexandre Reuben, Rachel M Gittelman, Jianjun Gao, Jiexin Zhang, Erik Yusko, Chang-Jiun Wu, Ryan Emerson, Jianhua Zhang, Christopher M Tipton, Jun Li, Kelly Quek, Vancheswaran Gopalakrishnan, Runzhe Chen, Luis Vence, Tina Cascone, Marissa Vignali, Junya Fujimoto, Jaime Rodriguez-Canales, Edwin R Parra, Latasha D Little, Curtis Gumbs, Marie-Andrée Forget, Lorenzo Federico, Cara Haymaker, Carmen Behrens, Sharon Benzeno, Chantale Bernatchez, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, William N William, Stephen G Swisher, John Heymach, Harlan Robins, J Jack Lee, Padmanee Sharma, James P Allison, P Andrew Futreal, Ignacio I Wistuba, Jianjun Zhang
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens were shown to alter tumor immunogenicity through T cell responses. Here, we performed sequencing of the T cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T cell density and clonality with the majority of T cell clones restricted to individual tumor regions...
July 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28731407/t-cell-receptor-repertoires-of-mice-and-humans-are-clustered-in-similarity-networks-around-conserved-public-cdr3-sequences
#13
Asaf Madi, Asaf Poran, Eric Shifrut, Shlomit Reich-Zeliger, Erez Greenstein, Irena Zaretsky, Tomer Arnon, Francois Van Laethem, Alfred Singer, Jinghua Lu, Peter D Sun, Irun R Cohen, Nir Friedman
Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#14
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28693542/overview-of-methodologies-for-t-cell-receptor-repertoire-analysis
#15
Elisa Rosati, C Marie Dowds, Evaggelia Liaskou, Eva Kristine Klemsdal Henriksen, Tom H Karlsen, Andre Franke
BACKGROUND: The T-cell receptor (TCR), located on the surface of T cells, is responsible for the recognition of the antigen-major histocompatibility complex, leading to the initiation of an inflammatory response. Analysing the TCR repertoire may help to gain a better understanding of the immune system features and of the aetiology and progression of diseases, in particular those with unknown antigenic triggers. The extreme diversity of the TCR repertoire represents a major analytical challenge; this has led to the development of specialized methods which aim to characterize the TCR repertoire in-depth...
July 10, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28693285/characterization-of-%C3%AE-%C3%AE-t-cells-in-patients-with-non-small-cell-lung-cancer
#16
Yi Bao, Li Guo, Juanfen Mo
Systemic immune defects that are associated with disease progression exist in a variety of malignancies. γδ T cells are innate-like lymphocytes that do not require self-major histocompatibility complex-restricted priming. Ex vivo-expanded circulating γδ T cells exhibit promising antitumor activity and are a potential candidate for the treatment of various malignancies, including non-small cell lung cancer (NSCLC). In the present study, flow cytometry was used as a method to study the phenotypes and characteristics of γδ T cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692065/increased-cathepsin-s-in-prdm1-dendritic-cells-alters-the-tfh-cell-repertoire-and-contributes-to-lupus
#17
Sun Jung Kim, Sebastian Schätzle, S Sohail Ahmed, Wolfgang Haap, Su Hwa Jang, Peter K Gregersen, George Georgiou, Betty Diamond
Aberrant population expansion of follicular helper T cells (TFH cells) occurs in patients with lupus. An unanswered question is whether an altered repertoire of T cell antigen receptors (TCRs) is associated with such expansion. Here we found that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant chains and produces antigenic peptides for loading onto major histocompatibility complex (MHC) class II molecules...
July 10, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28687658/the-effect-of-inhibitory-signals-on-the-priming-of-drug-hapten-specific-t-cells-that-express-distinct-v%C3%AE-receptors
#18
Andrew Gibson, Lee Faulkner, Maike Lichtenfels, Monday Ogese, Zaid Al-Attar, Ana Alfirevic, Philipp R Esser, Stefan F Martin, Munir Pirmohamed, B Kevin Park, Dean J Naisbitt
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28683116/persisting-fetal-clonotypes-influence-the-structure-and-overlap-of-adult-human-t-cell-receptor-repertoires
#19
Mikhail V Pogorelyy, Yuval Elhanati, Quentin Marcou, Anastasiia L Sycheva, Ekaterina A Komech, Vadim I Nazarov, Olga V Britanova, Dmitriy M Chudakov, Ilgar Z Mamedov, Yury B Lebedev, Thierry Mora, Aleksandra M Walczak
The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28662714/recall-t-cell-responses-to-bluetongue-virus-produce-a-narrowing-of-the-t-cell-repertoire
#20
José-Manuel Rojas, Teresa Rodríguez-Calvo, Noemí Sevilla
In most viral infections, recall T cell responses are critical for protection. The magnitude of these secondary responses can also affect the CD8 and CD4 epitope repertoire diversity. Bluetongue virus (BTV) infection in sheep elicits a T cell response that contributes to viremia control and could be relevant for cross-protection between BTV serotypes. Here, we characterized CD4(+) and CD8(+) T cell responses during primary and recall responses. During primary immune responses, both CD4(+) and CD8(+) T cell populations expanded by 14 days post-infection (dpi)...
June 29, 2017: Veterinary Research
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