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self reactive T cell

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https://www.readbyqxmd.com/read/28820075/t-regulatory-cell-subsets-in-children-with-type-1-diabetes-mellitus-relation-to-control-of-the-disease
#1
Mabrouk Ghonaim, Rawhia El-Edel, Wafaa Abo El Fotoh, Samar Kamal Eldein, Samar Salman
BACKGROUND: Type 1 diabetes mellitus described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are numbers of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance accomplished by thymic gland via a negative assortment of different clones while a dominant tolerance accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28806642/circulating-follicular-helper-t-cells-presented-distinctively-different-responses-toward-bacterial-antigens-in-primary-biliary-cholangitis
#2
Zun-Qiang Zhou, Da-Nian Tong, Jiao Guan, Mei-Fang Li, Qi-Ming Feng, Min-Jie Zhou, Zheng-Yun Zhang
Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4(+)CXCR5(+) follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4(+)CXCR5(+) T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype...
August 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28801345/molecular-basis-for-increased-susceptibility-of-indigenous-north-americans-to-seropositive-rheumatoid-arthritis
#3
Stephen W Scally, Soi-Cheng Law, Yi Tian Ting, Jurgen van Heemst, Jeremy Sokolove, Aaron J Deutsch, E Bridie Clemens, Antonis K Moustakas, George K Papadopoulos, Diane van der Woude, Irene Smolik, Carol A Hitchon, David B Robinson, Elizabeth D Ferucci, Charles N Bernstein, Xiaobo Meng, Vidyanand Anaparti, Tom Huizinga, Katherine Kedzierska, Hugh H Reid, Soumya Raychaudhuri, René E Toes, Jamie Rossjohn, Hani El-Gabalawy, Ranjeny Thomas
OBJECTIVE: The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28754892/a-cell-based-high-throughput-screening-assay-system-for-inhibitor-compounds-of-antigen-presentation-by-hla-class-ii-molecule
#4
Nobuo Watanabe, Yusuke Suzuki, Takahisa Yonezu, Yuki Nakagawa, Takashi Shiina, Noriaki Hirayama, Sadaki Inokuchi, Shigeaki Inoue
A number of autoimmune diseases are associated with the genotypes of human leukocyte antigen class II (HLA), some of which present peptides derived from self-proteins, resulting in clonal expansion of self-reactive T cells. Therefore, selective inhibition of self-peptide loading onto such disease-associated HLA could ameliorate the diseases. To effectively identify such compounds, in this study, we established, for the first time, a cell- and 96-well microplate-based high-throughput screening system for inhibitors of antigen presentation...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751760/il28b-rs12979860-genotype-as-a-predictor-marker-of-progression-to-bkvirus-associated-nephropathy-after-kidney-transplantation
#5
Roee Dvir, Vera Paloschi, Filippo Canducci, Giacomo Dell'Antonio, Sara Racca, Rossana Caldara, Giuseppe Pantaleo, Massimo Clementi, Antonio Secchi
BK virus (BKV) associated nephropathy (BKVAN) is still an important cause of allograft dysfunction after kidney transplantation (KT). Recent data have shown that the new interferon (IFN)-λ family has been ascribed antiviral properties similar to IFNα, and that the response to IFNλ in kidney is restricted to epithelial cells, suggesting that the IFNλ system evolves as specific protection of the epithelia. We aimed to test the hypothesis of correlation between a single nucleotide polymorphism (C/T dimorphism rs12979860) in the genomic region of IL28B and BKVAN, in patients after KT...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745239/therapeutic-interventions-of-tissue-specific-autoimmune-onset-in-systemic-lupus-erythematosus
#6
Subhajit Dasgupta
Systemic lupus erythematosus (SLE) is a female predominant autoimmune disease. The onset of SLE has been found to affect kidney, bone, cardiovascular and central nervous system. Auto activation of B cells and T helper cells together are known to develop self-reactive immune responses in SLE. The therapy still includes corticosteroids to prevent allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit to control disease manifestations...
July 25, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#7
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/28731407/t-cell-receptor-repertoires-of-mice-and-humans-are-clustered-in-similarity-networks-around-conserved-public-cdr3-sequences
#8
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/28711866/identification-of-apob-100-peptide-specific-cd8-t-cells-in-atherosclerosis
#9
Paul C Dimayuga, Xiaoning Zhao, Juliana Yano, Wai Man Lio, Jianchang Zhou, Peter M Mihailovic, Bojan Cercek, Prediman K Shah, Kuang-Yuh Chyu
BACKGROUND: T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. METHODS AND RESULTS: A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K(b) was used to generate a fluorescent-labeled H2K(b) pentamer and tested in apoE(-/-) mice...
July 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28704602/defective-early-b-cell-tolerance-checkpoints-in-sj%C3%A3-gren-s-syndrome-patients
#10
Salome Glauzy, Joel Sng, Jason Bannock, Jacques-Eric Gottenberg, Anne-Sophie Korganow, Patrice Cacoub, David Saadoun, Eric Meffre
OBJECTIVE: Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in SS patients. METHODS: Using a PCR-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19(+) CD21(low) CD10(+) IgM(hi) CD27(-) new emigrant/transitional and CD19(+) CD21(+) CD10(-) IgM(+) CD27(-) mature naïve B cells from five SS patients...
July 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#11
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28676527/the-id-genotype-of-mdm2-40-bp-insertion-deletion-polymorphism-was-associated-with-lower-risk-of-sle
#12
Saeedeh Salimi, Mahnaz Rezaei, Abbas Mohammadpour-Gharehbagh, Mojtaba Sajadian, Mahnaz Sandoughi
BACKGROUND: In patients with systemic lupus erythematosus (SLE), loss of immunological tolerance to self-nuclear antigens and abnormal activation of self-reactive T and B cells lead to self-antibodies and immune complex production. The autoreactive lymphocytes are removed by the apoptotic process in healthy individuals; however, apoptosis disruption could cause accumulation of apoptotic bodies and nuclear debris. Therefore, apoptosis plays a crucial role in the pathogenesis of autoimmune diseases...
July 4, 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28673572/elimination-of-cancer-stem-cells-and-reactivation-of-latent-hiv-1-via-ampk-activation-common-mechanism-of-action-linking-inhibition-of-tumorigenesis-and-the-potential-eradication-of-hiv-1
#13
Jahahreeh Finley
Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28664612/autoimmune-arthritis-induces-paired-immunoglobulin-like-receptor-b-expression-on-cd4-t%C3%A2-cells-from-skg-mice
#14
Kathrin Rothe, Nora Raulien, Gabriele Köhler, Matthias Pierer, Dagmar Quandt, Ulf Wagner
The chronic, destructive autoimmune arthritis in SKG mice, which closely resembles human rheumatoid arthritis, is the result of self-reactive T cells escaping thymic deletion. Since the inhibitory receptor LIR-1 is up-regulated on auto-reactive T cells in human rheumatoid arthritis, the role of its murine ortholog PIR-B was investigated. Peripheral CD4(+) T cells from SKG mice were found to frequently express PIR-B, and this population produces more frequently IL-17 upon in vitro stimulation compared to PIR-B(-) cells...
June 30, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28659353/alterations-in-the-thymic-selection-threshold-skew-the-self-reactivity-of-the-tcr-repertoire-in-neonates
#15
Mengqi Dong, Patricio Artusa, Stephanie A Kelly, Marilaine Fournier, Troy A Baldwin, Judith N Mandl, Heather J Melichar
Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652101/salt-inflammatory-joint-disease-and-autoimmunity
#16
Johanna Sigaux, Luca Semerano, Guillaume Favre, Natacha Bessis, Marie-Christophe Boissier
Salt is a vital nutrient. Excess salt intake, however, has recently been blamed for triggering and/or worsening certain autoimmune diseases. In vitro, the cells involved in innate and adaptive immune responses exhibit an inflammatory profile when placed in hypertonic saline. More specifically, macrophages release increased amounts of proinflammatory cytokines, produce reactive oxygen species, and become capable of activating the inflammasome. T helper cells, via activation of serum and glucocorticoid-regulated kinase 1 (SGK1), overexpress IL-17A and IL-23R and differentiate into Th17 cells; whereas regulatory T cells lose the inhibitory capabilities needed to preserve self-tolerance...
June 23, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28650341/two-rheumatoid-arthritis-specific-autoantigens-correlate-microbial-immunity-with-autoimmune-responses-in-joints
#17
Annalisa Pianta, Sheila L Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#18
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28632714/the-multiple-pathways-to-autoimmunity
#19
REVIEW
Argyrios N Theofilopoulos, Dwight H Kono, Roberto Baccala
Efforts to understand autoimmunity have been pursued relentlessly for several decades. It has become apparent that the immune system evolved multiple mechanisms for controlling self-reactivity, and defects in one or more of these mechanisms can lead to a breakdown of tolerance. Among the multitude of lesions associated with disease, the most common seem to affect peripheral tolerance rather than central tolerance. The initial trigger for both systemic autoimmune disorders and organ-specific autoimmune disorders probably involves the recognition of self or foreign molecules, especially nucleic acids, by innate sensors...
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28625883/tcr-cd3-cd4-cd8-effector-t-cells-in-psoriasis
#20
D Brandt, M Sergon, S Abraham, K Mäbert, C M Hedrich
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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