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Costimulatory t cells

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https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#1
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#2
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#3
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752615/effects-of-simvastatin-on-the-function-of-splenic-cd4-and-cd8-t-cells-in-sepsis-mice
#4
Bingbing Kong, Xiaofeng Wang, Wenping Yang, Xin Zhao, Rong Zhang, Yu Wang
Simvastatin may be beneficial for treating sepsis due to its immune-regulating properties, although the mechanisms remain elusive. Herein, we hypothesized simvastatin may attenuate T cell dysfunction induced by sepsis. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pre-treated with simvastatin (0.2 μg/g of body weight) before CLP. The expression of B and T lymphocyte attenuator (BTLA) on splenic CD4+ T cells and T cell apoptosis, CD4+ and CD8+ T cells were quantified by flow cytometry...
May 11, 2018: Immunologic Research
https://www.readbyqxmd.com/read/29752063/proteomic-analyses-of-human-regulatory-t-cells-reveal-adaptations-in-signaling-pathways-that-protect-cellular-identity
#5
Eloy Cuadrado, Maartje van den Biggelaar, Sander de Kivit, Yi-Yen Chen, Manon Slot, Ihsane Doubal, Alexander Meijer, Rene A W van Lier, Jannie Borst, Derk Amsen
To obtain a molecular definition of regulatory T (Treg) cell identity, we performed proteomics and transcriptomics on various populations of human regulatory and conventional CD4+ T (Tconv) cells. A protein expression signature was identified that defines all Treg cells, and another signature that defines effector Treg cells. These signatures could not be extrapolated from transcriptome data. Unique cell-biological and metabolic features in Treg cells were defined, as well as specific adaptations in cytokine, TCR, and costimulatory receptor signaling pathways...
May 5, 2018: Immunity
https://www.readbyqxmd.com/read/29751636/design-synthesis-and-evaluation-of-novel-immunomodulatory-small-molecules-targeting-the-cd40%C3%A2-cd154-costimulatory-protein-protein-interaction
#6
Damir Bojadzic, Jinshui Chen, Oscar Alcazar, Peter Buchwald
We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29749649/transgelin-2-in-immunity-its-implication-in-cell-therapy
#7
REVIEW
Suin Jo, Hye-Ran Kim, YeVin Mun, Chang-Duk Jun
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages...
May 11, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29743314/cd8-follicular-t-cells-promote-b-cell-antibody-class-switch-in-autoimmune-disease
#8
Kristen M Valentine, Dan Davini, Travis J Lawrence, Genevieve N Mullins, Miguel Manansala, Mufadhal Al-Kuhlani, James M Pinney, Jason K Davis, Anna E Beaudin, Suzanne S Sindi, David M Gravano, Katrina K Hoyer
CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29740438/the-nkg2d-nkg2dl-axis-in-the-crosstalk-between-lymphoid-and-myeloid-cells-in-health-and-disease
#9
REVIEW
Ana Stojanovic, Margareta P Correia, Adelheid Cerwenka
Natural killer group 2, member D (NKG2D) receptor is a type II transmembrane protein expressed by both innate and adaptive immune cells, including natural killer (NK) cells, CD8+ T cells, invariant NKT cells, γδ T cells, and some CD4+ T cells under certain pathological conditions. NKG2D is an activating NK receptor that induces cytotoxicity and production of cytokines by effector cells and supports their proliferation and survival upon engagement with its ligands. In both innate and T cell populations, NKG2D can costimulate responses induced by other receptors, such as TCR in T cells or NKp46 in NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29736404/-mycobacterium-tuberculosis-protein-rv3841-activates-dendritic-cells-and-contributes-to-a-t-helper-1-immune-response
#10
Seunga Choi, Han-Gyu Choi, Ki-Won Shin, Yong Woo Back, Hye-Soo Park, Jae Hwi Lee, Hwa-Jung Kim
The attenuated vaccine Mycobacterium bovis BCG (Bacille Calmette Guerin) has limited protective efficacy against TB. The development of more effective TB vaccines has focused on the mycobacterial antigens that cause strong T helper 1 (Th1) responses. Mtb protein Rv3841 (bacterioferritin B; BfrB) is known to play a crucial role in the growth of Mtb. Nonetheless, it is unclear whether Rv3841 can induce protective immunity against Mtb. Here, we studied the action of Rv3841 in maturation of dendritic cells (DCs) and its engagement in the development of T-cell immunity...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29727246/strategies-for-enhancing-adoptive-t-cell-immunotherapy-against-solid-tumors-using-engineered-cytokine-signaling-and-other-modalities
#11
Thomas Shum, Robert L Kruse, Cliona M Rooney
Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms...
May 4, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29722021/differential-tcr-signals-for-t-helper-cell-programming
#12
REVIEW
Penelope A Morel
Upon encounter with their cognate antigen naïve CD4 T cells become activated and are induced to differentiate into several possible T helper (Th) cell subsets. This differentiation depends on a number of factors including antigen presenting cells, cytokines and costimulatory molecules. The strength of the T cell receptor (TCR) signal, related to the affinity of TCR for antigen and antigen dose, has emerged as a dominant factor in determining Th cell fate. Recent studies have revealed that TCR signals of high or low strength do not simply induce quantitatively different signals in the T cells, but rather qualitatively distinct pathways can be induced based on TCR signal strength...
May 2, 2018: Immunology
https://www.readbyqxmd.com/read/29716982/hallmarks-of-t-cell-exit-from-quiescence
#13
Nicole M Chapman, Hongbo Chi
The appropriate activation of the adaptive immune system relies upon the reprogramming of naïve T cells into specialized effector T cells that can combat pathogens and tumors. Naïve T cells are actively maintained in a state of hyporesponsiveness termed quiescence, which is characterized by small cell size, low proliferative rate, and low basal metabolism. Engagement of antigen and costimulatory receptors drives T cells to exit quiescence to promote subsequent clonal expansion and functional differentiation...
May 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29709495/morphological-changes-induced-by-intraprostatic-psa-based-vaccine-in-prostate-cancer-biopsies-phase-i-clinical-trial
#14
Maria J Merino, A Peter, Vanessa Moreno, Sara Gil, Jeffrey Schlom, James L Gulley
Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostatic-specific antigen (PSA)-based vaccine. This study evaluated the histopathological effects in prostate biopsies of recombinant fowlpox (rF) virus-based vaccine engineered to present the PSA and three costimulatory molecules (collectively labeled as PSA-TRICOM). This vaccine has shown that it can break tolerance of the PSA, and its administration directly into a tumor enables the affected tumor cells to act as antigen-presenting cells activating new T-cells, and broadening the immune response to recognize and kill tumor...
April 27, 2018: Human Pathology
https://www.readbyqxmd.com/read/29701246/early-programming-and-late-acting-checkpoints-governing-the-development-of-cd4-t-cell-memory
#15
REVIEW
Kunal Dhume, K Kai McKinstry
CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T cell generation into vaccine strategies thus offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains...
April 27, 2018: Immunology
https://www.readbyqxmd.com/read/29697355/genetic-variation-of-costimulatory-molecules-including-cytotoxic-t-lymphocyte-antigen-4-inducible-t-cell-costimulator-cluster-differentiation-28-and-programmed-cell-death-1-genes-in-iranian-patients-with-leukemia
#16
Mani Ramzi, Nargess Arandi, Mahdiyar Iravani Saadi, Ramin Yaghobi, Bita Geramizadeh
OBJECTIVES: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods...
April 26, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29696308/role-of-mda5-and-interferon-i-in-dendritic-cells-for-t-cell-expansion-by-anti-tumor-peptide-vaccines-in-mice
#17
Hussein Sultan, Juan Wu, Takumi Kumai, Andres M Salazar, Esteban Celis
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion...
April 25, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29693595/the-costimulatory-pathways-and-t-regulatory-cells-in-ischemia-reperfusion-injury-a-strong-arm-in-the-inflammatory-response
#18
REVIEW
Laura de Ramon, Jordi Guiteras, Roser Guiteras, Josep M Cruzado, Josep M Grinyó, Juan Torras
Costimulatory molecules have been identified as crucial regulators in the inflammatory response in various immunologic disease models. These molecules are classified into four different families depending on their structure. Here, we will focus on various ischemia studies that use costimulatory molecules as a target to reduce the inherent inflammatory status. Furthermore, we will discuss the relevant role of T regulatory cells in these inflammatory mechanisms and the costimulatory pathways in which they are involved...
April 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29691900/a-dual-immunotherapy-nanoparticle-improves-t-cell-activation-and-cancer-immunotherapy
#19
Yu Mi, Christof C Smith, Feifei Yang, Yanfei Qi, Kyle C Roche, Jonathan S Serody, Benjamin G Vincent, Andrew Z Wang
Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death-1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal T-cell activation is achieved when both immunomodulatory agents simultaneously engage T-cells and promote synergistic proactivation signaling...
April 25, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29686687/coreceptors-and-their-ligands-in-epithelial-%C3%AE-%C3%AE-t-cell-biology
#20
REVIEW
Deborah A Witherden, Margarete D Johnson, Wendy L Havran
Epithelial tissues line the body providing a protective barrier from the external environment. Maintenance of these epithelial barrier tissues critically relies on the presence of a functional resident T cell population. In some tissues, the resident T cell population is exclusively comprised of γδ T cells, while in others γδ T cells are found together with αβ T cells and other lymphocyte populations. Epithelial-resident γδ T cells function not only in the maintenance of the epithelium, but are also central to the repair process following damage from environmental and pathogenic insults...
2018: Frontiers in Immunology
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