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Cytotoxic T cell

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https://www.readbyqxmd.com/read/29677476/cd4-helper-and-cd8-cytotoxic-t-cell-differentiation
#1
Ichiro Taniuchi
A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages. The MHC specificity of αβ T cell receptors (TCRs) on precursors is closely correlated with cell fate-determining processes, prompting studies to characterize how variations in TCR signaling are linked with genetic programs establishing lineage-specific gene expression signatures, such as exclusive CD4 or CD8 expression. The key transcription factors ThPOK and Runx3 have been identified as mediating development of helper and cytotoxic T cell lineages, respectively...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677457/improved-protocol-for-simultaneous-analysis-of-leukocyte-subsets-and-epithelial-cells-from-murine-and-human-lung
#2
Christine Happle, Lena Meyer-Decking, Anika Dreier, Martin Wetzke, Stephanie Gläsener, Ruth Grychtol, Peter Braubach, Alexandra Jablonka, Sibylle Haid, Adan Chari Jirmo, Anika Habener, Jelena Skuljec, Gesine Hansen
PURPOSE: To study and isolate lung cells by flow cytometry, enzymatic digestion and generation of single cell suspensions is required. This significantly influences expression of cellular epitopes and protocols need to be adapted for the best isolation and subsequent analysis of specific cellular subsets. MATERIALS AND METHODS: We optimized protocols for the simultaneous isolation and characterization of specific human and murine lung cell types. For alveolar epithelial cells (AEC), a primarily dispase based digestion method and for leukocytes, a primarily collagenase based technique was adapted...
April 20, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29677149/prior-puma-lentivirus-infection-modifies-early-immune-responses-and-attenuates-feline-immunodeficiency-virus-infection-in-cats
#3
Wendy S Sprague, Ryan M Troyer, Xin Zheng, Britta A Wood, Martha Macmillian, Scott Carver, Susan VandeWoude
We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4⁺ T cell preservation, greater interferon gamma (IFN-γ) mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection...
April 20, 2018: Viruses
https://www.readbyqxmd.com/read/29674728/physiological-function-of-phospholipase-d2-in-anti-tumor-immunity-regulation-of-cd8-t-lymphocyte-proliferation
#4
Van Ngo Thai Bich, Tsunaki Hongu, Yuki Miura, Naohiro Katagiri, Norihiko Ohbayashi, Yumi Yamashita-Kanemaru, Akira Shibuya, Yuji Funakoshi, Yasunori Kanaho
Two major phospholipase D (PLD) isozymes in mammals, PLD1 and PLD2, hydrolyze the membrane phospholipid phosphatidylcholine to choline and the lipid messenger phosphatidic acid. Although their roles in cancer cells have been well studied, their functions in tumor microenvironment have not yet been clarified. Here, we demonstrate that PLD2 in cytotoxic CD8+ T cells plays a crucial role in anti-tumor immunity by regulating their cell proliferation. We found that growth of tumors formed by subcutaneously transplanted cancer cells is enhanced in Pld2-knockout mice...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674635/design-synthesis-biological-activity-and-structure-activity-relationship-studies-of-chalcone-derivatives-as-potential-anti-candida-agents
#5
Jéssica T Andrade, Felipe R S Santos, William G Lima, Carla D F Sousa, Lohanna S F M Oliveira, Rosy I M A Ribeiro, Ana J P S Gomes, Marcelo G F Araújo, José A F P Villar, Jaqueline M S Ferreira
Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp...
April 19, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29674449/induction-of-antitumor-cytotoxic-lymphocytes-using-engineered-human-primary-blood-dendritic-cells
#6
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29673240/the-major-role-of-nf-kb-in-the-depth-of-invasion-on-acral-melanoma-by-decreasing-cd8-t-cells
#7
Hermin Aminah Usman, Bethy S Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani
Background: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor кB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response...
April 20, 2018: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/29673068/molecular-definition-of-the-transplantation-antigens
#8
REVIEW
Peter Parham
In the first half of the twentieth century, the Major Histocompatibility Complex (MHC) of the laboratory mouse, the H-2 complex, was defined by a combination of serology and genetics. In the second half of the twentieth century, its human counterpart, the Human Leukocyte Antigen (HLA) complex was similarly defined and shown to mediate rejection of allogeneic kidney grafts. The clinical relevance of the transplantation antigens created the field of transplant immunology, which aimed to reduce graft rejection by HLA matching of transplant donors and recipients, and to use immunosuppressive drugs to prevent and treat rejection...
April 19, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29672601/expression-of-immune-checkpoint-regulators-cytotoxic-t-lymphocyte-antigen-4-ctla-4-and-programmed-death-ligand-1-pd-l1-in-female-breast-carcinomas
#9
Ari Kassardjian, Peter I Shintaku, Neda A Moatamed
BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining...
2018: PloS One
https://www.readbyqxmd.com/read/29670880/targeting-tumor-associated-macrophages-as-a-potential-strategy-to-enhance-the-response-to-immune-checkpoint-inhibitors
#10
REVIEW
Luca Cassetta, Takanori Kitamura
Inhibition of immune checkpoint pathways in CD8+ T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8+ T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29670848/-teucrium-polium-extract-enhances-the-anti-angiogenesis-effect-of-tranilast-on-human-umbilical-vein-endothelial-cells
#11
Fatemeh Sheikhbahaei, Mozafar Khazaei, Seyed Noureddin Nematollahi-Mahani
Purpose: Angiogenesis plays an important role in numerous pathophysiological events like cancer. As a result of this, tranilast as an anti-fibrotic drug induces the promising antitumor activities through the inhibition of angiogenesis. Further, Teucrium polium (TP) is a herbal medicine (family Lamaceae) with antitumor properties. This study was conducted to investigate the combination effects of tranilast and T. polium on human umbilical vein endothelial cells (HUVECs) viability and apoptotic genes expression...
March 2018: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29670624/photochemical-internalization-of-peptide-antigens-provides-a-novel-strategy-to-realize-therapeutic-cancer-vaccination
#12
Markus Haug, Gaute Brede, Monika Håkerud, Anne Grete Nedberg, Odrun A Gederaas, Trude H Flo, Victoria T Edwards, Pål K Selbo, Anders Høgset, Øyvind Halaas
Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670239/resistance-of-hiv-infected-macrophages-to-cd8-t-lymphocyte-mediated-killing-drives-activation-of-the-immune-system
#13
Kiera L Clayton, David R Collins, Josh Lengieza, Musie Ghebremichael, Farokh Dotiwala, Judy Lieberman, Bruce D Walker
CD4+ T lymphocytes are the principal target of human immunodeficiency virus (HIV), but infected macrophages also contribute to viral pathogenesis. The killing of infected cells by CD8+ cytotoxic T lymphocytes (CTLs) leads to control of viral replication. Here we found that the killing of macrophages by CTLs was impaired relative to the killing of CD4+ T cells by CTLs, and this resulted in inefficient suppression of HIV. The killing of macrophages depended on caspase-3 and granzyme B, whereas the rapid killing of CD4+ T cells was caspase independent and did not require granzyme B...
May 2018: Nature Immunology
https://www.readbyqxmd.com/read/29670088/a-cancer-vaccine-mediated-postoperative-immunotherapy-for-recurrent-and-metastatic-tumors
#14
Tingting Wang, Dangge Wang, Haijun Yu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Shi Jiao, Yaping Li
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29669829/incomplete-downregulation-of-cd4-expression-affects-hiv-1-env-conformation-and-adcc-responses
#15
Jérémie Prévost, Jonathan Richard, Halima Medjahed, Audrey Alexander, Jennifer Jones, John C Kappes, Christina Ochsenbauer, Andrés Finzi
HIV-1 infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surface are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and HIV+ sera. By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMC) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669806/targeting-merkel-cell-carcinoma-by-engineered-t-cells-specific-to-t-antigens-of-merkel-cell-polyomavirus
#16
Ioannis Gavvovidis, Matthias Leisegang, Gerald Willimsky, Natalie J Miller, Paul Nghiem, Thomas Blankenstein
PURPOSE: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials...
April 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29669753/pilot-trial-of-ibrutinib-in-patients-with-relapsed-or-refractory-t-cell-lymphoma
#17
Anita Kumar, Santosha Vardhana, Alison J Moskowitz, Pierluigi Porcu, Ahmet Dogan, Jason A Dubovsky, Matthew J Matasar, Zhigang Zhang, Anas Younes, Steven M Horwitz
Ibrutinib has previously been shown to inhibit Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively. BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies. Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown. We hypothesized that ibrutinib-mediated ITK inhibition in T-cell lymphoma would result in decreased signaling through the T-cell receptor pathway and promote antitumor immune response by driving selective cytotoxic Th1 CD4 effector T-cell differentiation...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29669721/ppar-%C3%AE-contributes-to-immunity-by-cancer-vaccines-that-secrete-gm-csf
#18
Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
April 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29669249/the-transcription-factor-runx3-establishes-chromatin-accessibility-of-cis-regulatory-landscapes-that-drive-memory-cytotoxic-t-lymphocyte-formation
#19
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29669241/goldirunx-and-remembering-cytotoxic-memory
#20
Yohei Mikami, Yuka Kanno
The molecular basis for T cell memory differentiation remains elusive. Wang et al. (2018) identify Runx3 as an initiating transcription factor that specifies regulatory regions required for cytotoxic T cell (CTL) memory differentiation early after TCR signaling and constrains the ability of T-bet to drive terminal effector generation.
April 17, 2018: Immunity
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