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https://www.readbyqxmd.com/read/29020680/hepatic-t-cell-tolerance-induction-in-an-inflammatory-environment
#1
Janine Dywicki, Fatih Noyan, Ana Clara Misslitz, Martin Hapke, Melanie Galla, Jerome Schlue, Roland S Liblau, Richard Taubert, Michael P Manns, Elmar Jaeckel, Matthias Hardtke-Wolenski
For the development of autoimmune hepatitis (AIH), genetic predisposition and environmental triggers are of major importance. Although experimental AIH can be induced in genetically susceptible mice, the low precursor frequency of autoreactive T cells hampers a deeper analysis of liver-specific T cells. Here, we established a system where the model antigen hemagglutinin (HA) is expressed exclusively in hepatocytes of Rosa26-HA mice following administration of a replication deficient adenovirus expressing Cre recombinase (Ad-Cre)...
October 12, 2017: Digestive Diseases
https://www.readbyqxmd.com/read/28968466/changes-in-the-cellular-microrna-profile-by-the-intracellular-expression-of-hiv-1-tat-regulator-a-potential-mechanism-for-resistance-to-apoptosis-and-impaired-proliferation-in-hiv-1-infected-cd4-t-cells
#2
María Sánchez-Del Cojo, María Rosa López-Huertas, Francisco Díez-Fuertes, Sara Rodríguez-Mora, Mercedes Bermejo, Guillermo López-Campos, Elena Mateos, Laura Jiménez-Tormo, Francisco Gómez-Esquer, Gema Díaz-Gil, José Alcamí, Mayte Coiras
HIV-1 induces changes in the miRNA expression profile of infected CD4+ T cells that could improve viral replication. HIV-1 regulator Tat modifies the cellular gene expression and has been appointed as an RNA silencing suppressor. Tat is a 101-residue protein codified by two exons that regulates the elongation of viral transcripts. The first exon of Tat (amino acids 1-72) forms the transcriptionally active protein Tat72, but the presence of the second exon (amino acids 73-101) results in a more competent regulatory protein (Tat101) with additional functions...
2017: PloS One
https://www.readbyqxmd.com/read/28947542/nur77-regulates-nondeletional-mechanisms-of-tolerance-in-t-cells
#3
Qian Nancy Hu, Alexander Y W Suen, Laura M Henao Caviedes, Troy A Baldwin
Negative selection against highly self-reactive thymocytes is critical for preventing autoimmunity. Thymocyte deletion, anergy induction, and agonist selection are all forms of negative selection that can occur following a high-affinity TCR signal. Of Bim and Nur77, two TCR-induced proteins with proapoptotic function, Bim has been shown to be important for clonal deletion in several model systems, whereas Nur77 was often dispensable. However, Nur77 has been reported to influence other aspects of T cell development by mechanisms that may not be related to its proapoptotic function...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28942020/cd25-expressing-th17-cells-mediate-cd8-t-cell-suppression-in-ctla-4-dependent-mechanisms-in-pancreatic-ductal-adenocarcinoma
#4
Cuicui Lang, Jinyan Wang, Lei Chen
The tumor-associated immune response is governed by the signalling events of various regulatory molecules, one of which is the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). In conventional T cells, CTLA-4 could outcompete CD28 in binding to CD80/86 but does not produce a co-stimulatory signal, resulting in T cell anergy. CTLA-4 in regulatory T cells (Tregs) could also function in a cell-extrinsic fashion by removing CD80/CD86 from the antigen-presenting cells (APCs), thus preventing further priming of other T cells...
September 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#5
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#6
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
September 14, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#7
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900667/ammonium-trichloro-1-2-ethanediolato-o-o-tellurate-cures-experimental-visceral-leishmaniasis-by-redox-modulation-of-leishmania-donovani-trypanothione-reductase-and-inhibiting-host-integrin-linked-pi3k-akt-pathway
#8
Preeti Vishwakarma, Naveen Parmar, Pragya Chandrakar, Tanuj Sharma, Manoj Kathuria, Pramod K Agnihotri, Mohammad Imran Siddiqi, Kalyan Mitra, Susanta Kar
In an endeavor to search for affordable and safer therapeutics against debilitating visceral leishmaniasis, we examined antileishmanial potential of ammonium trichloro [1,2-ethanediolato-O,O']-tellurate (AS101); a tellurium based non toxic immunomodulator. AS101 showed significant in vitro efficacy against both Leishmania donovani promastigotes and amastigotes at sub-micromolar concentrations. AS101 could also completely eliminate organ parasite load from L. donovani infected Balb/c mice along with significant efficacy against infected hamsters (˃93% inhibition)...
September 12, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28887632/multipeptide-coupled-nanoparticles-induce-tolerance-in-humanised-hla-transgenic-mice-and-inhibit-diabetogenic-cd8-t-cell-responses-in-type-1-diabetes
#9
Xinyu Xu, Lingling Bian, Min Shen, Xin Li, Jing Zhu, Shuang Chen, Lei Xiao, Qingqing Zhang, Heng Chen, Kuanfeng Xu, Tao Yang
AIMS/HYPOTHESIS: Induction of antigen-specific immunological tolerance may provide an attractive immunotherapy in the NOD mouse model but the conditions that lead to the successful translation to human type 1 diabetes are limited. In this study, we covalently linked 500 nm carboxylated polystyrene beads (PSB) with a mixture of immunodominant HLA-A*02:01-restricted epitopes (peptides-PSB) that may have high clinical relevance in humans as they promote immune tolerance; we then investigated the effect of the nanoparticle-peptide complexes on T cell tolerance...
September 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28886586/a-murine-ig-light-chain-transgene-reveals-igkv3-gene-contributions-to-anti-collagen-types-iv-and-ii-specificities
#10
Amy G Clark, Inge M Worni-Schudel, Francesca M Korte, Mary H Foster
A subset of autoimmune diseases result from autoantibodies targeting epitopes on matrix collagen. The most extensively studied are anti-glomerular basement membrane glomerulonephritis (or its systemic counterpart Goodpasture's disease) that destroys kidneys and lungs, and rheumatoid arthritis that leads to disabling arthritis. Autoantibodies in these disorders bind evolutionarily conserved conformational epitopes on the noncollagenous domain 1 (NC1) of the alpha3 chain of type IV [alpha3(IV)NC1] collagen in glomerular and alveolar basement membranes, and on native or citrullinated type II collagen (CII) in joint cartilage, respectively...
September 5, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28878331/the-immunosuppressive-effect-of-the-tick-protein-salp15-is-long-lasting-and-persists-in-a-murine-model-of-hematopoietic-transplant
#11
Julen Tomás-Cortázar, Itziar Martín-Ruiz, Diego Barriales, Miguel Ángel Pascual-Itoiz, Virginia Gutiérrez de Juan, Alfredo Caro-Maldonado, Nekane Merino, Alberto Marina, Francisco J Blanco, Juana María Flores, James D Sutherland, Rosa Barrio, Adriana Rojas, María Luz Martínez-Chantar, Arkaitz Carracedo, Carolina Simó, Virginia García-Cañas, Leticia Abecia, José Luis Lavín, Ana M Aransay, Héctor Rodríguez, Juan Anguita
Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872140/purification-of-the-membrane-compartment-for-endoplasmic-reticulum-associated-degradation-of-exogenous-antigens-in-cross-presentation
#12
Jun Imai, Mayu Otani, Takahiro Sakai, Shinichi Hatta
Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8(+) T cells and memory CD8(+) T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28864471/peripheral-deletion-of-cd8-t-cells-requires-p38-mapk-in-cross-presenting-dendritic-cells
#13
Trevor Smith, Xiaotian Lin, Marielle Mello, Kristi Marquardt, Jocelyn Cheung, Binfeng Lu, Linda A Sherman, Grégory Verdeil
Peripheral tolerance mechanisms exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion. Dominant tolerance imposed by CD4(+)Foxp3(+) T regulatory cells can actively control autoaggressive T cell responses. Tolerance mechanisms that act endogenous to the T cell also exist. These mechanisms include T cell inactivation (anergy) and deletion. A major difference between anergic T cells and T cells undergoing peripheral deletion is the capacity of the latter to still signal through MAPKs upon TCR stimulation, suggesting these signals may be required for T deletion...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28860938/early-growth-response-2-and-egr3-are-unique-regulators-in-immune-system
#14
REVIEW
Sina Taefehshokr, Yashar Azari Key, Mansour Khakpour, Pourya Dadebighlu, Amin Oveisi
The immune system is evolved to defend the body against pathogens and is composed of thousands of complicated and intertwined pathways, which are highly controlled by processes such as transcription and repression of cellular genes. Sometimes the immune system malfunctions and a break down in self-tolerance occurs. This lead to the inability to distinguish between self and non-self and cause attacks on host tissues, a condition also known as autoimmunity, which can result in chronic debilitating diseases. Early growth response genes are family of transcription factors comprising of four members, Egr1, Egr2, Egr3 and Egr4...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28774470/history-and-mechanisms-of-oral-tolerance
#15
REVIEW
Rafael M Rezende, Howard L Weiner
Since its first description by Wells and Osbourne in 1911, oral tolerance has intrigued researchers due to its potential for therapeutic applications. Oral tolerance can be defined as an inhibition of specific immune responsiveness to subsequent parenteral injections of proteins to which an individual or animal has been previously exposed via the oral route. Tolerance induction to commensal bacteria and dietary proteins represents the major immunological event taking place in the gut in physiological conditions...
April 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#16
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28758047/the-role-of-the-ikaros-family-of-transcription-factors-in-regulatory-t-cell-development-and-function
#17
Amara Seng, Thomas M Yankee
Regulatory T (Treg) cells are a subset of immune cells that maintain homeostasis by promoting immune tolerance and suppressing the immune response via a variety of mechanisms such as secreting cytokines, killing reactive immune cells, and inducing anergy. Dysfunction of Treg cells has been implicated in inflammatory diseases such as autoimmunity and transplant rejection. Conversely, too many or hyperresponsive Treg cells has been observed in cancer and chronic infections. Treg cells have proven to be difficult to study as there are no definitive Treg surface markers...
April 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28732688/molecular-pathophysiology-of-gout
#18
REVIEW
Jyaysi Desai, Stefanie Steiger, Hans-Joachim Anders
Three contradictory clinical presentations of gout have puzzled clinicians and basic scientists for some time: first, the crescendo of sterile inflammation in acute gouty arthritis; second, its spontaneous resolution, despite monosodium urate (MSU) crystal persistence in the synovium; and third, immune anergy to MSU crystal masses observed in tophaceous or visceral gout. Here, we provide an update on the molecular pathophysiology of these gout manifestations, namely, how MSU crystals can trigger the auto-amplification loop of necroinflammation underlying the crescendo of acute gouty arthritis...
July 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28670575/cd8-memory-t-cell-inflation-renders-compromised-cd4-t-cell-dependent-cd8-t-cell-immunity-via-na%C3%A3-ve-t-cell-anergy
#19
Aizhang Xu, Andrew Freywald, Yufeng Xie, Zejun Li, Jim Xiang
Whether inflation of CD8(+) memory T (mT) cells, which is often derived from repeated prime-boost vaccinations or chronic viral infections in the elderly, would affect late CD8(+) T-cell immunity is a long-standing paradox. We have previously established an animal model with mT-cell inflation by transferring ConA-stimulated monoclonal CD8(+) T cells derived from Ova-specific T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice. In this study, we also established another two animal models with mT-cell inflation by transferring, 1) ConA-stimulated monoclonal CD8(+) T cells derived from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8(+) T cells derived from B6...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28638849/refractory-t-cell-anergy-and-rapidly-fatal-progressive-multifocal-leukoencephalopathy-after-prolonged-ctla4-therapy
#20
Manon Dekeyser, Marie-Ghislaine de Goër de Herve, Houria Hendel-Chavez, Céline Labeyrie, David Adams, Ghaïdaa Adebs Nasser, Jacques Gasnault, Antoine Durrbach, Yassine Taoufik
Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease due to central nervous system replication of the human polyomavirus JC virus (JCV) in immunosuppressed patients. The only effective therapeutic approach is to restore anti-JCV T-cell responses. In this study, we describe a case of rapidly fatal PML with JCV T-cell anergy in a renal transplant patient treated with CTLA4-Ig (belatacept, a CD28-B7 costimulation blocker and T-cell anergy inducer). T-cell anergy could not be reversed despite several therapeutic approaches...
2017: Open Forum Infectious Diseases
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