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self reactive T cell

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https://www.readbyqxmd.com/read/29335648/rapid-chromatin-repression-by-aire-provides-precise-control-of-immune-tolerance
#1
Andrew S Koh, Erik L Miller, Jason D Buenrostro, David M Moskowitz, Jing Wang, William J Greenleaf, Howard Y Chang, Gerald R Crabtree
Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance against self-reactive T lymphocytes. However, the mechanism that allows expression of tissue-specific genes at levels that prevent harm is unknown. Here we show that Brg1 generates accessibility at tissue-specific loci to impose central tolerance. We found that Aire has an intrinsic repressive function that restricts chromatin accessibility and opposes Brg1 across the genome. Aire exerted this repressive influence within minutes after recruitment to chromatin and restrained the amplitude of active transcription...
January 15, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29321275/cd40-mediates-maturation-of-thymic-dendritic-cells-driven-by-self-reactive-cd4-thymocytes-and-supports-development-of-natural-regulatory-t-cells
#2
Jaehak Oh, Nan Wu, Andrea J Barczak, Rebecca Barbeau, David J Erle, Jeoung-Sook Shin
Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4+ thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29311380/hitting-the-target-how-t-cells-detect-and-eliminate-tumors
#3
REVIEW
Anthony E Zamora, Jeremy Chase Crawford, Paul G Thomas
The successes of antitumor immuno-based therapies and the application of next-generation sequencing to mutation profiling have produced insights into the specific targets of antitumor T cells. Mutated proteins have tremendous potential as targets for interventions using autologous T cells or engineered cell therapies and may serve as important correlates of efficacy for immunoregulatory interventions including immune checkpoint blockade. As mutated self, tumors present an exceptional case for host immunity, which has primarily evolved in response to foreign pathogens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29311365/simultaneous-recognition-of-allogeneic-mhc-and-cognate-autoantigen-by-autoreactive-t-cells-in-transplant-rejection
#4
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29305419/the-molecular-basis-of-immune-regulation-in-autoimmunity
#5
REVIEW
Shu-Han Yang, Cai-Yue Gao, Liang Li, Christopher Chang, Patrick S C Leung, M Eric Gershwin, Zhe-Xiong Lian
Autoimmune diseases can be triggered and modulated by various molecular and cellular characteristics. The mechanisms of autoimmunity and the pathogenesis of autoimmune diseases have been investigated for several decades. It is well accepted that autoimmunity is caused by dysregulated/dysfunctional immune susceptible genes and environmental factors. There are multiple physiological mechanisms that regulate and control self-reactivity, but which can also lead to tolerance breakdown when in defect. The majority of autoreactive T or B cells are eliminated during the development of central tolerance by negative selection...
January 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29288206/il-4-induced-gene-1-a-negative-immune-checkpoint-controlling-b-cell-differentiation-and-activation
#6
Lloyd Bod, Laetitia Douguet, Cédric Auffray, Renée Lengagne, Fériel Bekkat, Elena Rondeau, Valérie Molinier-Frenkel, Flavia Castellano, Yolande Richard, Armelle Prévost-Blondel
Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29285060/inhibitory-effect-of-oxidative-damage-on-cardiomyocyte-differentiation-from-wharton-s-jelly-derived-mesenchymal-stem-cells
#7
Natakarn Nimsanor, Jitrada Phetfong, Chotiros Plabplueng, Kulachart Jangpatarapongsa, Virapong Prachayasittikul, Aungkura Supokawej
Ischemic heart diseases are a serious health problem worldwide. The transplantation of mesenchymal stem cells (MSCs) has been investigated in numerous clinical trials on various other diseases due to the self-renewal capacity of these cells and their potential to differentiate into a variety of cell types. The presence of excess reactive oxygen species in injured myocardium causes cardiac dysfunction and leads to inefficient repair of the heart. The poor outcomes of stem cell transplantation have been suggested to result from residual oxidative damage affecting the transplanted cells...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29284181/clinical-validation-of-a-novel-elispot-based-in-vitro-diagnostic-assay-to-monitor-cmv-specific-cell-mediated-immunity-in-kidney-transplant-recipients-a-multicenter-longitudinal-prospective-observational-study
#8
Bernhard Banas, Dominik Steubl, Lutz Renders, Dominik Chittka, Miriam C Banas, Thomas Wekerle, Martina Koch, Oliver Witzke, Anja Mühlfeld, Claudia Sommerer, Antje Habicht, Christian Hugo, Thomas Hünig, Monika Lindemann, Traudel Schmidt, Anne Rascle, Sascha Barabas, Ludwig Deml, Ralf Wagner, Bernhard K Krämer, Bernd Krüger
Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of CMV reactivation and associated complications in solid-organ transplantation. Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T-Track® CMV, a novel IFN-γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE-I CMV proteins, to monitor CMV-CMI following kidney transplantation...
December 28, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29282307/cutting-edge-low-affinity-tcrs-support-regulatory-t-cell-function-in-autoimmunity
#9
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29276180/cd40-knocked-down-tolerogenic-dendritic-cells-decrease-diabetic-injury
#10
Aziz Mahmoudzadeh, Ali Akbar Pourfathollah, Mohammad Hossein Karimi, Seyed Mohammad Moazzeni
BACKGROUND: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. OBJECTIVE: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. METHODS: Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29260623/pd-1-pd-l1-in-disease
#11
Nyanbol Kuol, Lily Stojanovska, Kulmira Nurgali, Vasso Apostolopoulos
AIM: Expression of PD-1 on T/B cells regulates peripheral tolerance and autoimmunity. Binding of PD-1 to its ligand, PD-L1, leads to protection against self-reactivity. In contrary, tumor cells have evolved immune escape mechanisms whereby overexpression of PD-L1 induces anergy and/or apoptosis of PD-1 positive T cells by interfering with T cell receptor signal transduction. PD-L1 and PD-1 blockade using antibodies are in human clinical trials as an alternative cancer treatment modality...
February 2018: Immunotherapy
https://www.readbyqxmd.com/read/29251415/specific-t-cell-responses-against-minor-histocompatibility-antigens-cannot-generally-be-explained-by-absence-of-their-allelic-counterparts-on-the-cell-surface
#12
Helena Maria Bijen, Chopie Hassan, Michel G D Kester, George M C Janssen, Pleun Hombrink, Arnoud H de Ru, Jan Wouter Drijfhout, Hugo D Meiring, Ad P de Jong, J H Frederik Falkenburg, Connie R Jimenez, Mirjam H M Heemskerk, Peter A van Veelen
Allogeneic stem cell transplantation has emerged as immunotherapy in the treatment of a variety of hematological malignancies. Its efficacy depends on induction of graft versus leukemia by donor lymphocytes. Both graft versus leukemia and graft versus host disease are induced by T-cells reactive against polymorphic peptides, called minor histocompatibility antigens (MiHA), which differ between patient and donor and are presented in the context of self-HLA. The allelic counterpart (AC) of the MiHA is generally considered to be absent at the cell surface, based on the absence of immune responses directed against the AC...
December 18, 2017: Proteomics
https://www.readbyqxmd.com/read/29247045/the-immunology-of-hypertension
#13
REVIEW
Allison E Norlander, Meena S Madhur, David G Harrison
Although systemic hypertension affects a large proportion of the population, its etiology remains poorly defined. Emerging evidence supports the concept that immune cells become activated and enter target organs, including the vasculature and the kidney, in this disease. Mediators released by these cells, including reactive oxygen species, metalloproteinases, cytokines, and antibodies promote dysfunction of the target organs and cause damage. In vessels, these factors enhance constriction, remodeling, and rarefaction...
December 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29239722/calcium-mediated-shaping-of-naive-cd4-t-cell-phenotype-and-function
#14
Vincent Guichard, Nelly Bonilla, Aurélie Durand, Alexandra Audemard-Verger, Thomas Guilbert, Bruno Martin, Bruno Lucas, Cédric Auffray
Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on Calcineurin activation...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29237773/a-subset-of-human-autoreactive-cd1c-restricted-t-cells-preferentially-expresses-trbv4-1-tcrs
#15
Tingxi Guo, Ming Yin Koo, Yuki Kagoya, Mark Anczurowski, Chung-Hsi Wang, Kayoko Saso, Marcus O Butler, Naoto Hirano
In humans, a substantial portion of T cells recognize lipids presented by the monomorphic CD1 proteins. Recent studies have revealed the molecular basis of mycobacterial lipid recognition by CD1c-restricted T cells. Subsets of CD1c-restricted T cells recognize self-lipids in addition to foreign lipids, which may have implications in human diseases involving autoimmunity and malignancy. However, the molecular identity of these self-reactive T cells remains largely elusive. In this study, using a novel CD1c+ artificial APC (aAPC)-based system, we isolated human CD1c-restricted autoreactive T cells and characterized them at the molecular level...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29234108/mother-to-newborn-transmission-of-mycobacterial-l-forms-and-v%C3%AE-2-t-cell-response-in-placentobiome-of-bcg-vaccinated-pregnant-women
#16
T Dimova, A Terzieva, L Djerov, V Dimitrova, A Nikolov, P Grozdanov, N Markova
The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L bacterial forms are extremely scarce. Bacille Calmette-Guérin is an attenuated strain of M. bovis and the only licensed vaccine used for tuberculosis prevention. We already have shown that filterable L-forms of BCG exist freely in the vaccine and are able to reproduce and to form colonies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217175/reactivity-of-igm-antibodies-elicited-by-pegylated-liposomes-or-pegylated-lipoplexes-against-auto-and-foreign-antigens
#17
Hidenori Ando, Amr S Abu Lila, Munehira Kawanishi, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, Tatsuhiro Ishida
Polyethylene glycol (PEG) is an attractive tool for the development of nanoparticle-based cancer therapy since it endows nanoparticles with extended-circulation properties. Nevertheless, recent reports have revealed that intravenous injection of either PEGylated liposomes (SLs) or PEGylated lipoplex (PLpx) could elicit an anti-PEG immunoglobulin (IgM) response in a T cell-independent (TI) manner that would substantially compromise the in vivo fate of PEGylated products upon repeated administration. In the same context, viral or bacterial infections trigger the production of polyreactive IgM that binds both self and foreign antigens...
December 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29202179/extensively-reorganized-systemic-lymph-nodes-provide-a-feasible-environment-for-self-reactivity-in-lupus-prone-nzb-nzw-f1-mice
#18
Yoichi Kurosawa, Madoka Ozawa, Yasuhiro Kanda, Arata Takeuchi, Toshihiko Kawamura, Ichiei Narita, Tomoya Katakai
Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue reorganization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T cell area, and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis...
November 30, 2017: International Immunology
https://www.readbyqxmd.com/read/29187854/an-analysis-of-natural-t-cell-responses-to-predicted-tumor-neoepitopes
#19
Anne-Mette Bjerregaard, Morten Nielsen, Vanessa Jurtz, Carolina M Barra, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of cancer immunotherapies such as therapeutic vaccines and adoptive T-cell therapy may benefit from efficient identification and targeting of patient-specific neoepitopes. However, current neoepitope prediction methods based on sequencing and predictions of epitope processing and presentation result in a low rate of validation, suggesting that the determinants of peptide immunogenicity are not well understood. We gathered published data on human neopeptides originating from single amino acid substitutions for which T cell reactivity had been experimentally tested, including both immunogenic and non-immunogenic neopeptides...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163476/induction-of-peripheral-tolerance-in-ongoing-autoimmune-inflammation-requires-interleukin-27-signaling-in-dendritic-cells
#20
Rodolfo Thomé, Jason N Moore, Elisabeth R Mari, Javad Rasouli, Daniel Hwang, Satoshi Yoshimura, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad M Rostami
Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG35-55 after onset of disease to induce i...
2017: Frontiers in Immunology
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