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https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#1
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
#2
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
#3
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
#4
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/28878331/the-immunosuppressive-effect-of-the-tick-protein-salp15-is-long-lasting-and-persists-in-a-murine-model-of-hematopoietic-transplant
#5
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
#6
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
#7
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...
September 1, 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
#8
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/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
#9
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
#10
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/28670575/cd8-memory-t-cell-inflation-renders-compromised-cd4-t-cell-dependent-cd8-t-cell-immunity-via-na%C3%A3-ve-t-cell-anergy
#11
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
#12
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
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#13
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28628673/multiple-tolerance-defects-contribute-to-the-breach-of-b-cell-tolerance-in-new-zealand-black-chromosome-1-congenic-mice
#14
Nan-Hua Chang, Kieran P Manion, Christina Loh, Evelyn Pau, Yuriy Baglaenko, Joan E Wither
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy...
2017: PloS One
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#15
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed "anergy", is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28599122/respiratory-syncytial-virus-infection-compromises-asthma-tolerance-by-recruiting-interleukin-17a-producing-cells-via-ccr6-ccl20-signaling
#16
Tianyun Shi, Yanchao He, Wei Sun, Yi Wu, Ling Li, Zhijun Jie, Xiao Su
Asthma tolerance can be induced by breast-feeding or oral feeding with ovalbumin (OVA). Anergy or deletion of specific T cells and generation of T regulatory cells might contribute to this process. However, whether respiratory syncytial virus (RSV) infection would affect asthma tolerance is not very clear. Here, we first established asthma and oral tolerance mouse models and then analyzed airway hypersensitivity and asthma-related genes in the lung, CCR6-expressing IL-17A(+) cells in the lungs, hilar or mesenteric lymph nodes (HLN or MLN) among control, asthmatic, tolerized, RSV infection, and RSV-infected asthmatic and tolerized groups...
June 6, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28576496/identification-of-zinc-finger-transcription-factor-egr2-as-a-novel-acetylated-protein
#17
Kota Noritsugu, Akihiro Ito, Yoichi Nakao, Minoru Yoshida
EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28572627/microrna-150-modulates-intracellular-ca-2-levels-in-na%C3%A3-ve-cd8-t-cells-by-targeting-tmem20
#18
Tae-Don Kim, Hong-Ryul Jung, Sang-Hwan Seo, Se-Chan Oh, Youngho Ban, Xiaoxia Tan, Jung Min Kim, Sang Hyun Lee, Duk-Su Koh, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Junsang Doh, Sang-Jun Ha, Inpyo Choi, Philip D Greenberg
Regulation of intracellular Ca(2+) signaling is a major determinant of CD8(+) T cell responsiveness, but the mechanisms underlying this regulation of Ca(2+) levels, especially in naïve CD8(+) T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca(2+) levels in naïve CD8(+) T cells required for activation by suppressing TMEM20, a negative regulator of Ca(2+) extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca(2+) levels in naïve CD8(+) T cells...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#19
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/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#20
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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