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https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#1
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28324181/trigeminocardiac-reflex-during-endoscopic-juvenile-nasopharyngeal-angiofibroma-surgery-an-appraisal
#2
Shilpee Bhatia Sharma, Trichy Narayanan Janakiram, Hina Baxi, Balamurugan Chinnasamy
Juvenile nasopharyngeal angiofibroma is a locally aggressive benign tumour which has propensity to erode the skull base. The tumour spreads along the pathways of least resistance and is in close proximity to the extracranial part of trigeminal nerve. Advancements in expanded approaches for endoscopic excision of tumours in infratemporal fossa and pterygopalatine fossa increase the vulnerability for the trigeminocardiac reflex. The manipulation of nerve and its branches during tumour dissection can lead to sensory stimulation and thus inciting the reflex...
March 21, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28323289/clonality-testing-of-lymphoproliferative-disorders-in-a-large-cohort-of-primary-and-consultant-biopsies
#3
Michaela Svachova, Martin Tichy, Patrik Flodr, Jana Steigerova, Zdenek Kolar, Jan Bouchal
BACKGROUND: Lymphoproliferative disease often presents the clinician and pathologist with a diagnostic dilemma, particularly in the early course of the disease. METHODS: We used modified BIOMED-2 protocols to detect monoclonal expansions of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) genes in 957 formalin-fixed paraffin-embedded samples from 717 patients. To eliminate false-positive results, heteroduplex analysis was used after PCR reactions. The impact of different fixatives on DNA quality and performance of PCR was assessed...
March 14, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28323276/open-capsule-budesonide-for-refractory-celiac-disease
#4
Saurabh S Mukewar, Ayush Sharma, Alberto Rubio-Tapia, Tsung-Teh Wu, Bana Jabri, Joseph A Murray
OBJECTIVES: Refractory celiac disease (RCD) is a rare condition often associated with poor prognosis. Various immunosuppressive medications (IMs) have been used with modest success. We describe outcomes in patients treated with open-capsule budesonide (OB), including those for whom IM treatment failed. METHODS: We identified RCD patients treated with OB at Mayo Clinic, Rochester, Minnesota from 2003 to 2015. Demographic, serologic, and clinical variables were analyzed...
March 21, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#5
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28320914/two-strikes-and-you-re-out-the-pathogenic-interplay-of-coinhibitor-deficiency-and-lymphopenia-induced-proliferation
#6
REVIEW
Kristofor K Ellestad, Colin C Anderson
Lymphopenia-induced proliferation (LIP) occurs when resources for T cell survival in a host are in excess. LIP has been associated with the development of inflammatory disease in situations where an additional disease-predisposing cofactor is present during LIP. This has led to the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability to precipitate autoimmunity and we have recently shown that in some circumstances, such as the absence of the coinhibitory molecule PD-1, additional hits are required...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#7
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/28318800/autoimmune-disease-development-based-on-possible-mislocalization-of-intracellular-and-extracellular-proteins
#8
Borros Arneth
BACKGROUND: T helper cells can differentiate into several subsets of T lymphocytes, including Th1, Th2, and regulatory T (Treg) cells. As a result of this ability to differentiate, the corresponding T cell receptor (TCR) spectra display considerable cellular plasticity and interchangeability. In contrast, T lymphocyte differentiation and separation into CD4(+) and/or CD8(+) T cell lines creates stable populations over a person's lifetime, which abrogates the plasticity and interchange between these cell types and their corresponding TCR spectra but results in considerable stability regarding the corresponding TCR sequences and spectra...
February 27, 2017: Immunobiology
https://www.readbyqxmd.com/read/28315222/tetramer-guided-epitope-mapping-a-rapid-approach-to-identify-hla-restricted-t-cell-epitopes-from-composite-allergens
#9
Luis L Diego Archila, William W Kwok
Tetramer-guided epitope mapping (TGEM) is a technique in immunology that permits the rapid identification of allergenic epitopes through peptide screening procedures utilizing human lymphocyte antigen (HLA) class II tetramers as staining reagents for detection. The identification of allergenic epitopes is a prerequisite for the accurate characterization of allergen-specific CD4(+) T cells without in vitro stimulation. Additionally, these MHC-II/peptide complexes that interact with T-cell receptors (TCR) of pathogenic CD4(+) T cells are compatible with a different number of assays like Intracelullar Cytokine Staining (ICS), and Carboxyfluorescein succinimidyl ester (CFSE) making it a robust technology to study the functionality of allergen-specific CD4(+) T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28314956/evolution-of-mhc-based-technologies-used-for-detection-of-antigen-responsive-t-cells
#10
REVIEW
Amalie Kai Bentzen, Sine Reker Hadrup
T cell-mediated recognition of peptide-major histocompatibility complex (pMHC) class I and II molecules is crucial for the control of intracellular pathogens and cancer, as well as for stimulation and maintenance of efficient cytotoxic responses. Such interactions may also play a role in the development of autoimmune diseases. Novel insights into this mechanism are crucial to understanding disease development and establishing new treatment strategies. MHC multimers have been used for detection of antigen-responsive T cells since the first report by Altman et al...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28314856/ubc9-is-required-for-positive-selection-and-late-stage-maturation-of-thymocytes
#11
Aibo Wang, Xiao Ding, Maud Demarque, Xindong Liu, Deng Pan, Huawei Xin, Bo Zhong, Xiaohu Wang, Anne Dejean, Wei Jin, Chen Dong
SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting Ubc9 gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of Ubc9 results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28301594/daxx-plays-a-novel-role-in-t-cell-survival-but-is-dispensable-in-fas-induced-apoptosis
#12
Jinghe Li, Liangyue Qian, John P Dowling, Christine Curcione, Drishya Kurup, Jianke Zhang
Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas...
2017: PloS One
https://www.readbyqxmd.com/read/28300170/cd8-t-cells-specific-for-the-islet-autoantigen-igrp-are-restricted-in-their-t-cell-receptor-chain-usage
#13
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/28298179/preparation-of-peptide-mhc-and-t-cell-receptor-dextramers-by-biotinylated-dextran-doping
#14
Michael T Bethune, Begoña Comin-Anduix, Yu-Hsien Hwang Fu, Antoni Ribas, David Baltimore
Peptide-major histocompatibility complex (pMHC) multimers enable the detection, characterization, and isolation of antigen-specific T-cell subsets at the single-cell level via flow cytometry and fluorescence microscopy. These labeling reagents exploit a multivalent scaffold to increase the avidity of individually weak T-cell receptor (TCR)-pMHC interactions. Dextramers are an improvement over the original streptavidin-based tetramer technology because they are more multivalent, improving sensitivity for rare, low-avidity T cells, including self/tumor-reactive clones...
March 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28296250/different-genetic-alteration-of-a20-in-a-s%C3%A3-zary-syndrome-case-with-v%C3%AE-2-j%C3%AE-22-t-cell-clone
#15
Lingling Zhou, Haitao Zheng, Xin Huang, Lihua Zhu, Suijing Wu, Chengwu Zeng, Lijian Yang, Shaohua Chen, Gengxin Luo, Xin Du, Yangqiu Li
BACKGROUND: The comprehensive genetic alterations underlying the pathogenesis of Sézary syndrome (SS) remains largely unknown. Previous studies showed that alterations of tumor necrosis factor-α-induced protein 3 gene (TNFAIP3; A20) are frequent in SS. In this study, we characterized the mutation and polymorphisms of A20 in a case with SS and compared with the genetic feature of A20 in T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Using a novel approach based on the combination of fine-tiling array comparative genomic hybridization ( and ligation-mediated polymerase chain reaction (LM-PCR) to identify SS clone, the polymorphisms in the A20 gene (promoter, exons 2-9 [coding region] and 3'UTR) were detected by PCR and sequencing...
March 14, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#16
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28290464/blocking-the-recruitment-of-naive-cd4-t-cells-reverses-immunosuppression-in-breast-cancer
#17
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...
March 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28289401/sleep-disorders-is-the-trigemino-cardiac-reflex-a-missing-link
#18
REVIEW
Tumul Chowdhury, Barkha Bindu, Gyaninder Pal Singh, Bernhard Schaller
Trigeminal innervated areas in face, nasolacrimal, and nasal mucosa can produce a wide array of cardiorespiratory manifestations that include apnea, bradypnea, bradycardia, hypotension, and arrhythmias. This reflex is a well-known entity called "trigemino-cardiac reflex" (TCR). The role of TCR is investigated in various pathophysiological conditions especially in neurosurgical, but also skull base surgery procedures. Additionally, its significance in various sleep-related disorders has also been highlighted recently...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28287509/using-x-ray-crystallography-biophysics-and-functional-assays-to-determine-the-mechanisms-governing-t-cell-receptor-recognition-of-cancer-antigens
#19
Bruce J MacLachlan, Alexander Greenshields-Watson, Georgina H Mason, Andrea J Schauenburg, Valentina Bianchi, Pierre J Rizkallah, Andrew K Sewell, Anna Fuller, David K Cole
Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings...
February 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286257/grouper-epinephelus-coioides-tcr-signaling-pathway-was-involved-in-response-against-cryptocaryon-irritans-infection
#20
Ze-Xiang Li, Yan-Wei Li, Shun Xu, Yang Xu, Ze-Quan Mo, Xue-Ming Dan, Xiao-Chun Luo
T cell activation is a complicated process accompanying with the activation of T cell receptor (TCR) signaling pathway, which is not well described in teleost fish. The initiation of this pathway depends on the interaction of membrane TCR co-receptors (e.g. CD4/8, CD3 and CD45) and a series of cytoplasmic protein tyrosine kinases (e.g. Lck, Fyn and ZAP70). Cyptocaryon irritans is a ciliate pathogen of marine fish white spot disease causing huge economic lost in marine aquaculture. This parasite can infect fish gill and skin and is considered to be a good pathogen model for fish gill and skin mucosal immunity...
March 7, 2017: Fish & Shellfish Immunology
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