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self reactive T cell

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https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#1
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27917626/association-of-new-putative-epitopes-of-myelin-proteolipid-protein-58-74-with-pathogenesis-of-multiple-sclerosis
#2
Zahra Zamanzadeh, Ghasem Ahangari, Mitra Ataei, Samie Pouragahi, Seyed Massood Nabavi, Mehdi Sadeghi, Mohammad Hossein Sanati
Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27904889/reactive-oxygen-species-in-bcr-abl1-expressing-cells-relevance-to-chronic-myeloid-leukemia
#3
Joanna Antoszewska-Smith, Elzbieta Pawlowska, Janusz Blasiak
Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis...
December 1, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#4
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902998/autoimmune-cytopenias-diagnosis-management
#5
Christian P Nixon, Joseph D Sweeney
The autoimmune cytopenias are a related group of disorders in which differentiated hematopoietic cells are destroyed by the immune system. Single lineage disease is characterized by the production of autoantibodies against red cells (autoimmune hemolytic anemia [AIHA]), platelets (autoimmune thrombocytopenia [ITP]) and neutrophils (autoimmune neutropenia [AIN]) whereas multilineage disease may include various combinations of these conditions. Central to the genesis of this disease is the breakdown of central and/or peripheral tolerance, and the subsequent production of autoantibodies by both tissue and circulating self-reactive B lymphocytes with support from T helper lymphocytes...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27894837/cd4-virtual-memory-antigen-inexperienced-t-cells-reside-in-the-na%C3%A3-ve-regulatory-and-memory-t-cell-compartments-at-similar-frequencies-implications-for-autoimmunity
#6
Alina I Marusina, Yoko Ono, Alexander A Merleev, Michiko Shimoda, Hiromi Ogawa, Elizabeth A Wang, Kayo Kondo, Laura Olney, Guillaume Luxardi, Yoshinori Miyamura, Tilahun D Yilma, Itzel Bustos Villalobos, Jennifer W Bergstrom, Daniel G Kronenberg, Athena M Soulika, Iannis E Adamopoulos, Emanual Maverakis
It is widely accepted that central and effector memory CD4(+) T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts...
November 25, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27891480/traumatic-ulcerative-granuloma-with-stromal-eosinophila-a-case-report-and-review-of-pathogenesis
#7
Bhushan Sharma, George Koshy, Shekhar Kapoor
Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is an uncommon condition considered to be a, reactive benign lesion of the oral mucosa, usually affecting the tongue. Its aetiopathogenesis is still uncertain. However, trauma has been found to be a contributing factor in a majority of the cases. Clinically, it often presents as an isolated ulcer or an indurated submucosal mass. Microscopically, it is characterized by a diffuse polymorphic cell infiltrate composed predominantly of eosinophils, B and T lymphocytes, macrophages, and large atypical cells involving the superficial mucosa and extending deep into the submucosa causing degeneration of the underlying muscle...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27891224/tcr-signaling-by-conventional-cd4-t-cells-is-required-for-optimal-maintenance-of-peripheral-regulatory-t-cell-numbers
#8
Theresa M Leichner, Atsushi Satake, Taku Kambayashi
To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin-2 (IL-2) and T cell receptor (TCR) stimulation by major histocompatibility complex class II (MHC-II). Here, we report that in addition to TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR signaling by Tconvs. We found that Tconvs produce IL-2 in response to self-peptide-MHC-II complexes and that Tconvs possessing more highly self-reactive TCRs express more IL-2 at baseline...
June 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27881740/peripheral-self-reactivity-regulates-antigen-specific-cd8-t-cell-responses-and-cell-division-under-physiological-conditions
#9
Lee Kim Swee, Zhen Wei Tan, Anna Sanecka, Nagisa Yoshida, Harshil Patel, Gijsbert Grotenbreg, Eva-Maria Frickel, Hidde L Ploegh
T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity-hence reactivity to self-and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2(b) haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L(d)-restricted epitope, derived from the Rop7 protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#10
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27843891/establishment-and-maintenance-of-the-human-na%C3%A3-ve-cd4-t-cell-compartment
#11
REVIEW
Susana L Silva, Ana E Sousa
The naïve CD4(+) T-cell compartment is considered essential to guarantee immune competence throughout life. Its replenishment with naïve cells with broad diverse receptor repertoire, albeit with reduced self-reactivity, is ensured by the thymus. Nevertheless, cumulative data support a major requirement of post-thymic proliferation both for the establishment of the human peripheral naïve compartment during the accelerated somatic growth of childhood, as well as for its lifelong maintenance. Additionally, a dynamic equilibrium is operating at the cell level to fine-tune the T-cell receptor threshold to activation and survival cues, in order to counteract the continuous naïve cell loss by death or conversion into memory/effector cells...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27834728/graft-versus-self-gvs-against-t-cell-autoantigens-is-a-mechanism-of-graft-host-interaction
#12
Nora Mirza, Manfred Zierhut, Andreas Korn, Antje Bornemann, Wichard Vogel, Barbara Schmid-Horch, Wolfgang A Bethge, Stefan Stevanović, Helmut R Salih, Lothar Kanz, Hans-Georg Rammensee, Sebastian P Haen
Graft-versus-host disease (GVHD) represents the major nonrelapse complication of allogeneic hematopoietic cell transplantation. Although rare, the CNS and the eye can be affected. In this study, manifestation in the retina as part of the CNS and T-cell epitopes recognized by the allogeneic T cells were evaluated. In 2 of 6 patients with posttransplantation retina diseases and 6 of 22 patients without ocular symptoms, antigen-specific T-cell responses against retina-specific epitopes were observed. No genetic differences between donor and recipient could be identified indicating T-cell activation against self-antigens (graft versus self)...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27829150/programmed-death-1-culls-peripheral-accumulation-of-high-affinity-autoreactive-cd4%C3%A2-t-cells-to-protect-against-autoimmunity
#13
Tony T Jiang, Tijana Martinov, Lijun Xin, Jeremy M Kinder, Justin A Spanier, Brian T Fife, Sing Sing Way
Self-reactive CD4 T cells are incompletely deleted during thymic development, and their peripheral seeding highlights the need for additional safeguards to avert autoimmunity. Here, we show an essential role for the coinhibitory molecule programmed death-1 (PD-1) in silencing the activation of high-affinity autoreactive CD4 T cells. Each wave of self-reactive CD4 T cells that escapes thymic deletion autonomously upregulates PD-1 to maintain self-tolerance. By tracking the progeny derived from individual autoreactive CD4 T cell clones, we demonstrate that self-reactive cells with the greatest autoimmune threat and highest self-antigen affinity express the most PD-1...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27823582/domain-swapped-t-cell-receptors-improve-the-safety-of-tcr-gene-therapy
#14
Michael T Bethune, Marvin H Gee, Mario Bunse, Mark S Lee, Eric H Gschweng, Meghana S Pagadala, Jing Zhou, Donghui Cheng, James R Heath, Donald B Kohn, Michael S Kuhns, Wolfgang Uckert, David Baltimore
T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses...
November 8, 2016: ELife
https://www.readbyqxmd.com/read/27798616/neutrophils-license-inkt-cells-to-regulate-self-reactive-mouse-b-cell-responses
#15
Thomas Hägglöf, Saikiran K Sedimbi, Jennifer L Yates, Roham Parsa, Briana Hauff Salas, Robert A Harris, Elizabeth A Leadbetter, Mikael C I Karlsson
The innate responsiveness of the immune system is important not only for quick responses to pathogens but also for the initiation and shaping of the subsequent adaptive immune response. Activation via the cytokine IL-18, a product of inflammasomes, gives rise to a rapid response that includes the production of self-reactive antibodies. As increased concentrations of this cytokine are found in inflammatory diseases, we investigated the origin of the B cell response and its regulation. We identified an accumulation of B cell-helper neutrophils in the spleen that interacted with innate-type invariant natural killer T cells (iNKT cells) to regulate B cell responses...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27798614/analysis-of-self-antigen-specificity-of-islet-infiltrating-t-cells-from-human-donors-with-type-1-diabetes
#16
Jenny Aurielle B Babon, Megan E DeNicola, David M Blodgett, Inne Crèvecoeur, Thomas S Buttrick, René Maehr, Rita Bottino, Ali Naji, John Kaddis, Wassim Elyaman, Eddie A James, Rachana Haliyur, Marcela Brissova, Lut Overbergh, Chantal Mathieu, Thomas Delong, Kathryn Haskins, Alberto Pugliese, Martha Campbell-Thompson, Clayton Mathews, Mark A Atkinson, Alvin C Powers, David M Harlan, Sally C Kent
A major therapeutic goal for type 1 diabetes (T1D) is to induce autoantigen-specific tolerance of T cells. This could suppress autoimmunity in those at risk for the development of T1D, as well as in those with established disease who receive islet replacement or regeneration therapy. Because functional studies of human autoreactive T cell responses have been limited largely to peripheral blood-derived T cells, it is unclear how representative the peripheral T cell repertoire is of T cells infiltrating the islets...
October 31, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27792880/redox-sensitive-cerium-oxide-nanoparticles-protect-human-keratinocytes-from-oxidative-stress-induced-by-glutathione-depletion
#17
Ragini Singh, Ajay Singh Karakoti, William T Self, Sudipta Seal, Sanjay Singh
Cerium oxide nanoparticles (CeNPs) have gathered much attention in the biomedical field due to its unique antioxidant property. It can protect cells and tissues from oxidative stress induced damage due to its auto-regenerative redox cycle. Our study explores the antioxidant and anti-genotoxic behaviour of PEGylated CeNPs towards oxidative insult produced by BSO (Buthionine sulfoximine) in human keratinocytes (HaCaT cells). BSO inhibits the γ-glutamylcysteinesynthetase (γ-GCS) enzyme and thus acts as a glutathione (GSH) depleting agent to modulate the cellular redox potential...
October 28, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27792294/weakly-self-reactive-t-cell-clones-can-homeostatically-expand-when-present-at-low-numbers
#18
Nienke Vrisekoop, Patricio Artusa, Joao P Monteiro, Judith N Mandl
T-cell division is central to maintaining a stable T-cell pool in adults. It also enables T-cell expansion in neonates, and after depletion by chemotherapy, bone marrow transplantation, or infection. The same signals required for T-cell survival in lymphoreplete settings, IL-7 and T-cell receptor (TCR) interactions with self-peptide MHC (pMHC), induce division when T-cell numbers are low. The strength of reactivity for self-pMHC has been shown to correlate with the capacity of T cells to undergo lymphopenia-induced proliferation (LIP), in that weakly self-reactive T cells are unable to divide, implying that T-cell reconstitution would significantly skew the TCR repertoire toward TCRs with greater self-reactivity and thus compromise T-cell diversity...
October 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27782066/boosting-tumor-specific-immunity-using-pdt
#19
REVIEW
Nicole Maeding, Thomas Verwanger, Barbara Krammer
Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators...
October 6, 2016: Cancers
https://www.readbyqxmd.com/read/27776339/generation-of-cd20-specific-tcrs-for-tcr-gene-therapy-of-cd20low-b-cell-malignancies-insusceptible-to-cd20-targeting-antibodies
#20
Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
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