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self reactive T cell

Tina M Mitre, Anmar Khadra, Massimo Pietropaolo
The expression level of tissue-restricted autoantigens (TSA) in the thymus is crucial for the negative selection of autoreactive T cells during central tolerance. The autoimmune regulator factor (AIRE) plays an important role in the positive regulation of these TSA in medullary thymic epithelial cells and, consequently, in the negative selection of high-avidity autoreactive T cells. Recent studies, however, revealed that thymic islet cell autoantigen (ICA69) expression level in non-obese diabetic (NOD) mice, prone to developing type 1 diabetes (T1D), is reduced due to an increase in the binding affinity of AIRE to the Ica1-promoter region, which regulates ICA69 protein synthesis...
October 17, 2016: Mathematical Biosciences
Vahid Davoudi, Kiandokht Keyhanian, Riley M Bove, Tanuja Chitnis
Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Sarah A Overall, Dorothée Bourges, Ian R van Driel, Paul A Gleeson
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice...
October 19, 2016: European Journal of Immunology
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
Ryuichi Morishita
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. We have designed DNA vaccine for the treatment of high blood pressure (BP) toward to human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats (SHR) using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months...
September 2016: Journal of Hypertension
Maria-Luisa Alegre, Fadi G Lakkis, Adrian E Morelli
Transplantation of solid organs between genetically distinct individuals leads, in the absence of immunosuppression, to T cell-dependent transplant rejection. Activation of graft-reactive T cells relies on the presentation of transplant-derived antigens (intact donor MHC molecules or processed peptides on host MHC molecules) by mature dendritic cells (DCs). This review focuses on novel insights regarding the steps for maturation and differentiation of DCs that are necessary for productive presentation of transplant antigens to host T cells...
October 12, 2016: Trends in Immunology
Qi Wang, Elise E Drouin, Chunxiang Yao, Jiyang Zhang, Yu Huang, Deborah R Leon, Allen C Steere, Catherine E Costello
HLA-DR-molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1,593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins...
October 11, 2016: Journal of Proteome Research
Jairo A Diaz, Mauricio F Murillo, Jhonan A Mendoza, Ana M Barreto, Lina S Poveda, Lina K Sanchez, Laura C Poveda, Katherine T Mora
Emergent biological responses develop via unknown processes dependent on physical collision. In hypoxia, when the tissue architecture collapses but the geometric core is stable, actin cytoskeleton filament components emerge, revealing a hidden internal order that identifies how each molecule is reassembled into the original mold, using one common connection, i.e., a fractal self-similarity that guides the system from the beginning in reverse metamorphosis, with spontaneous self-assembly of past forms that mimics an embryoid phenotype...
2016: American Journal of Stem Cells
Thilo Oelert, Amos Gilhar, Ralf Paus
The hair follicle (HF) epithelium can present self-antigens to cognate CD8+ T cells. These cells express periodically during the hair cycle arising or age-related immunogenic proteins including HF-specific neo-antigens. We propose, that IFN-gamma derived from the respective antigen-specific T cells spotting the particular self-peptides may thereby significantly induce and alter self-antigen presentation ("induced-self"). This induction, at first, may silence T cells, including neo-epitope-specific T cells. As the thymus cannot significantly recapitulate neo-epitopes evolving in the periphery, we propose that peripheral tissue-specific induction of MHC molecules presenting exactly these neo-epitopes by self- MHC/peptide-reactive CD8+ T cells is a key element of self-tolerance...
October 7, 2016: Experimental Dermatology
Nicholas R J Gascoigne, Vasily Rybakin, Oreste Acuto, Joanna Brzostek
Thymocyte selection involves the positive and negative selection of the repertoire of T cell receptors (TCRs) such that the organism does not suffer autoimmunity, yet has the benefit of the ability to recognize any invading pathogen. The signal transduced through the TCR is translated into a number of different signaling cascades that result in transcription factor activity in the nucleus and changes to the cytoskeleton and motility. Negative selection involves inducing apoptosis in thymocytes that express strongly self-reactive TCRs, whereas positive selection must induce survival and differentiation programs in cells that are more weakly self-reactive...
October 6, 2016: Annual Review of Cell and Developmental Biology
Carine Savarin, Cornelia C Bergmann, David R Hinton, Stephen A Stohlman
Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells...
2016: Frontiers in Immunology
Dibyendu Kumar Das, Robert J Mallis, Jonathan S Duke-Cohan, Rebecca E Hussey, Paul W Tetteh, Mark Hilton, Gerhard Wagner, Matthew J Lang, Ellis Reinherz
The pre-T cell receptor (preTCR) is a pTα-β heterodimer functioning in early αβ T-cell development. Although once thought to be ligand-autonomous, recent studies show that preTCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe preTCR bonding with pMHC at the single molecule level. Like the αβTCR, the preTCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes, and exploiting allosteric control regulated via the Cβ FG loop region...
October 5, 2016: Journal of Biological Chemistry
Gaurang Jhala, Jonathan Chee, Prerak M Trivedi, Claudia Selck, Esteban N Gurzov, Kate L Graham, Helen E Thomas, Thomas W H Kay, Balasubramanian Krishnamurthy
High-affinity self-reactive thymocytes are purged in the thymus, and residual self-reactive T cells, which are detectable in healthy subjects, are controlled by peripheral tolerance mechanisms. Breakdown in these mechanisms results in autoimmune disease, but antigen-specific therapy to augment natural mechanisms can prevent this. We aimed to determine when antigen-specific therapy is most effective. Islet autoantigens, proinsulin (PI), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) were expressed in the antigen-presenting cells (APCs) of autoimmune diabetes-prone nonobese diabetic (NOD) mice in a temporally controlled manner...
July 7, 2016: JCI Insight
Jaxaira Maggi, Katina Schinnerling, Bárbara Pesce, Catharien M Hilkens, Diego Catalán, Juan C Aguillón
Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells in an antigen-specific manner. For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4(+) T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs (mDCs), evaluating proliferation and cytokine production by flow cytometry...
2016: Frontiers in Immunology
Corinne J Smith, Michael Quinn, Christopher M Snyder
Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8(+) T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8(+) T cell immunity...
2016: Frontiers in Immunology
Ricardo García-Muñoz, Carlos Panizo
The ultimate cause of follicular lymphoma (FL) remains unknown. Remarkably, almost nothing is known about immunological tolerance mechanisms that might contribute to FL development. Immunological tolerance mechanisms, like other stimuli, also induce persistent changes of B cell receptors that induce genetic instability and molecular aberrations promoting the development of a neoplasm. Using the same method as Burnet, we provide a new perspective taking advantage of the comparison of a normal linear B cell differentiation process and FL development within the framework of clonal selection theory...
September 29, 2016: Human Immunology
Lorenz Jahn, Renate S Hagedoorn, Dirk M van der Steen, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
CD22 is currently evaluated as a target-antigen for the treatment of B-cell malignancies using chimeric antigen receptor (CAR)-engineered T-cells or monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been successfully applied targeting other antigens, however, occurrence of refractory disease to these interventions urges the identification of additional strategies. Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02...
September 26, 2016: Oncotarget
Periklis Dousdampanis, Kostantina Trigka, Athanasia Mouzaki
Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells...
September 24, 2016: World Journal of Transplantation
Laura F Su, Daniel Del Alcazar, Erietta Stelekati, E John Wherry, Mark M Davis
The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities of Tregs outside the context of transgenic TCRs are largely unknown. Using peptide-MHC tetramers, we isolated rare specific Foxp3(+) cells directly ex vivo from adult peripheral blood and defined their frequency and phenotype. We find that a proportion of circulating Tregs recognize foreign antigens and the frequency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
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