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Autoimmunity t cell

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https://www.readbyqxmd.com/read/28551826/development-of-an-8-color-antibody-panel-for-functional-phenotyping-of-human-cd8-cytotoxic-t-cells-from-peripheral-blood-mononuclear-cells
#1
Tara Patel, Amy Cunningham, Martha Holland, John Daley, Suzan Lazo, F Stephen Hodi, Mariano Severgnini
The study of CD8 positive cells in peripheral blood has become an essential part of research in the field of cancer immunotherapies, vaccine development, inflammation, autoimmune disease, etc. In this study, an 8-color flow cytometry panel, containing lineage and functional markers, was developed for the identification of CD8+ cytotoxic T cells in previously cryopreserved peripheral blood mononuclear cells from healthy human donors. By studying functional markers in naïve and CD3/CD28 activated T cells we demonstrate that the panel is capable of detecting protein markers corresponding to different T cell activation statuses...
May 27, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#2
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#3
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#4
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550204/cutting-edge-origins-recruitment-and-regulation-of-cd11c-cells-in-inflamed-islets-of-autoimmune-diabetes-mice
#5
Joanna E Klementowicz, Ashley E Mahne, Allyson Spence, Vinh Nguyen, Ansuman T Satpathy, Kenneth M Murphy, Qizhi Tang
In NOD mice, CD11c(+) cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c(+) cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c(+) cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c(+) cells was partially dependent on their receptor Ccr5...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550200/t-cells-deficient-in-the-tyrosine-phosphatase-shp-1-resist-suppression-by-regulatory-t-cells
#6
Emily R Mercadante, Ulrike M Lorenz
The balance between activation of T cells and their suppression by regulatory T cells (Tregs) is dysregulated in autoimmune diseases and cancer. Autoimmune diseases feature T cells that are resistant to suppression by Tregs, whereas in cancer, T cells are unable to mount antitumor responses due to the Treg-enriched suppressive microenvironment. In this study, we observed that loss of the tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, renders naive CD4(+) and CD8(+) T cells resistant to Treg-mediated suppression in a T cell-intrinsic manner...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550190/patient-derived-anti-%C3%AE-2gp1-antibodies-recognize-a-peptide-motif-pattern-and-not-a-specific-sequence-of-residues
#7
Philippe de Moerloose, Céline Fickentscher, Françoise Boehlen, Jean-Marie Tiercy, Egbert K O Kruithof, Karim J Brandt
Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the beta-2-glycoprotein 1 (β2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the present study, we wanted to identify a sequence in the domain I of β2GP1 able to induce the proliferation of CD4+ T cells isolated from antiphospholipid antibody syndrome patients but not from healthy donors and to interact with antiphospholipid antibodies...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#8
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
May 26, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#9
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28548588/injection-of-inactive-bordetella-pertussis-and-complete-freund-s-adjuvant-with-torpedo-californica-achr-increases-the-occurrence-of-experimental-autoimmune-myasthenia-gravis-in-c57bl-6-mice
#10
Takahiro Maruta, Minako Oshima, Dennis R Mosier, M Zouhair Atassi
An animal model of myasthenia gravis (MG), termed experimental autoimmune MG (EAMG), is an important tool for investigations of disease mechanisms and/or methods of treatment for this disease. EAMG can be induced in C57BL/6 (B6, H-2(b)) mice by 2-3 times injections at 4 weeks intervals with Torpedo californica (t) acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA). However, the protocol especially with a two-injection schedule occasionally produces a poor incidence of EAMG. We have investigated the efficacy of the additional adjuvant, inactive organisms of Bordetella pertussis (iBP), on the induction with a two-injection schedule...
May 26, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28548026/low-reliability-of-anti-kir4-183-120-peptide-auto-antibodies-in-multiple-sclerosis-patients
#11
Mariapaola Marino, Giovanni Frisullo, Gabriele Di Sante, Daniela Maria Samengo, Carlo Provenzano, Massimiliano Mirabella, Giovambattista Pani, Francesco Ria, Emanuela Bartoccioni
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease for which auto-antibodies fully validated as diagnostic and prognostic biomarkers are widely desired. Recently, an immunoreactivity against the inward rectifying potassium channel 4.1 (KIR4.1) has been reported in a large proportion of a group of MS patients, with amino acids 83-120 being the major epitope. Moreover, a strong correlation between anti-KIR4.183-120 and anti-full-length-protein auto-antibodies titer was reported...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#12
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546852/the-repeated-administration-of-resveratrol-has-measurable-effects-on-circulating-t-cell-subsets-in-humans
#13
J Luis Espinoza, Ly Quoc Trung, Pleiades T Inaoka, Kayoko Yamada, Dao T An, Shohei Mizuno, Shinji Nakao, Akiyoshi Takami
Preclinical studies have shown that resveratrol exerts immunomodulatory effects with potential clinical value in the amelioration of autoimmune disorders and cancer prevention; however, little is known about the in vivo effects of this naturally occurring polyphenol on human immune cells. We assessed the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy Japanese individuals. Resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating γδ T cells and regulatory T cells and resulted in small, yet significant, decreases in the plasma levels of the proinflammatory cytokines TNF-α and MCP-1 and a significant increase in the plasma antioxidant activity compared with the corresponding antioxidant baseline activity and with that in four control individuals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28546563/microbiota-in-t-cell-homeostasis-and-inflammatory-diseases
#14
REVIEW
Naeun Lee, Wan-Uk Kim
The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546444/glial-fibrillary-acidic-protein-gfap-is-a-novel-biomarker-for-the-prediction-of-autoimmune-diabetes
#15
Zhengda Pang, Akifumi Kushiyama, Jiao Sun, Takako Kikuchi, Hiroki Yamazaki, Yasuhiko Iwamoto, Hiroshi Koriyama, Shota Yoshida, Munehisa Shimamura, Masayoshi Higuchi, Tomohiro Kawano, Yoichi Takami, Hiromi Rakugi, Ryuichi Morishita, Hironori Nakagami
Glial fibrillary acidic protein (GFAP) is expressed in peri-islet Schwann cells as well as in glia cells and has been reported to be an autoantigen candidate for type 1 diabetes mellitus (T1DM). We confirmed that the production of the autoantibodies GFAP and glutamic acid decarboxylase 65 (GAD65) was increased and inversely correlated with the concentration of secreted C peptide in female nonobese diabetic mice (T1DM model). Importantly, the development of T1DM in female nonobese diabetic mice at 30 wk of age was predicted by the positive GFAP autoantibody titer at 17 wk...
May 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28546083/mechanisms-of-tolerance-and-potential-therapeutic-interventions-in-alopecia-areata
#16
REVIEW
Gabriel Skogberg, Sonya Jackson, Annika Åstrand
This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546003/thymic-epithelial-cell-specific-deletion-of-jmjd6-reduces-aire-protein-expression-and-exacerbates-disease-development-in-a-mouse-model-of-autoimmune-diabetes
#17
Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui
Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity...
May 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28545581/increased-serum-level-of-soluble-interleukin-2-receptor-is-associated-with-a-worse-response-of-metastatic-clear-cell-renal-cell-carcinoma-to-interferon-alpha-and-sequential-vegf-targeting-therapy
#18
Akinori Nukui, Akinori Masuda, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28542128/hmg-coa-reductase-promotes-protein-prenylation-and-therefore-is-indispensible-for-t-cell-survival
#19
Sonja M Lacher, Julia Bruttger, Bettina Kalt, Jean Berthelet, Krishnaraj Rajalingam, Simone Wörtge, Ari Waisman
Statins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541315/therapeutic-t-cell-engineering
#20
Michel Sadelain, Isabelle Rivière, Stanley Riddell
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape...
May 24, 2017: Nature
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