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Exhausted T cell

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https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#1
Nadine Honke, Namir Shaabani, Cornelia Hardt, Caroline Krings, Dieter Häussinger, Philipp A Lang, Karl S Lang, Verena Keitel
BACKGROUND: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. METHODS: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV)...
January 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#2
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#3
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198713/cd1d-restricted-natural-killer-t-cells-are-preserved-in-indian-long-term-non-progressors-ltnps
#4
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
BACKGROUND: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. METHODOLOGY: NKT cells were characterized for their frequency and the activation, aging, exhaustion status and their proliferation ability in 32 long term non progressors (LTNPs), 40 progressors, 18 patients before and after suppressive cART along with 35 HIV-1 negative subjects using multicolor flowcytometry...
February 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#5
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#6
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#7
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28193736/down-regulation-of-cd73-on-b-cells-of-patients-with-viremic-hiv-correlates-with-b-cell-activation-and-disease-progression
#8
Eun-Seong Kim, Christin Ackermann, Ilona Tóth, Patrick Dierks, Johanna M Eberhard, Raluca Wroblewski, Felix Scherg, Matthias Geyer, Reinhold E Schmidt, Claudia Beisel, Maximilian Bockhorn, Friedrich Haag, Jan van Lunzen, Julian Schulze Zur Wiesch
Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0...
February 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28179496/cutting-edge-chromatin-accessibility-programs-cd8-t-cell-memory
#9
Christopher D Scharer, Alexander P R Bally, Bhanu Gandham, Jeremy M Boss
CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#10
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28170385/exhausting-alloreactivity-of-donor-derived-car-t-cells
#11
Maksim Mamonkin, Helen E Heslop
No abstract text is available yet for this article.
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28165481/targeting-mitochondrial-dysfunction-can-restore-antiviral-activity-of-exhausted-hbv-specific-cd8-t-cells-in-chronic-hepatitis-b
#12
Paola Fisicaro, Valeria Barili, Barbara Montanini, Greta Acerbi, Manuela Ferracin, Francesca Guerrieri, Debora Salerno, Carolina Boni, Marco Massari, M Cristina Cavallo, Glenda Grossi, Tiziana Giuberti, Pietro Lampertico, Gabriele Missale, Massimo Levrero, Simone Ottonello, Carlo Ferrari
Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28163249/activation-and-exhaustion-of-antigen-specific-cd8-t-cells-occur-in-different-splenic-compartments-during-infection-with-plasmodium-berghei
#13
Ganchimeg Bayarsaikhan, Mana Miyakoda, Kazuo Yamamoto, Daisuke Kimura, Masoud Akbari, Masao Yuda, Katsuyuki Yui
The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8(+) T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8(+) T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection...
February 3, 2017: Parasitology International
https://www.readbyqxmd.com/read/28163164/anti-pd-1-pd-l1-therapy-for-infectious-diseases-learning-from-the-cancer-paradigm
#14
REVIEW
Martin Rao, Davide Valentini, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Immune checkpoint pathways regulate optimal host immune responses against transformed cells, induce immunological memory, and limit tissue pathology. Conversely, aberrant immune checkpoint activity signifies a poor prognosis in cancer and infectious diseases. Host-directed therapy (HDT) via immune checkpoint blockade has revolutionized cancer treatment with therapeutic implications for chronic infections, thus laying the foundation for this review. METHODS: Online literature searches were performed via PubMed, PubMed Central, and Google using the keywords "immune checkpoint inhibition"; "host-directed therapy"; "T cell exhaustion"; "cancer immunotherapy"; "anti-PD-1 therapy"; "anti-PD-L1 therapy"; "chronic infections"; "antigen-specific cells"; "tuberculosis"; "malaria"; "viral infections"; "human immunodeficiency virus"; "hepatitis B virus"; "hepatitis C virus"; "cytomegalovirus" and "Epstein-Barr virus"...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28160567/ews-fli1-confers-exquisite-sensitivity-to-nampt-inhibition-in-ewing-sarcoma-cells
#15
Cornelia N Mutz, Raphaela Schwentner, Dave N T Aryee, Eric D J Bouchard, Edgard M Mejia, Grant M Hatch, Maximilian O Kauer, Anna M Katschnig, Jozef Ban, Antje Garten, Javier Alonso, Versha Banerji, Heinrich Kovar
Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28158203/silymarin-suppresses-basal-and-stimulus-induced-activation-exhaustion-differentiation-and-inflammatory-markers-in-primary-human-immune-cells
#16
Erica S Lovelace, Nicholas J Maurice, Hannah W Miller, Chloe K Slichter, Robert Harrington, Amalia Magaret, Martin Prlic, Stephen De Rosa, Stephen J Polyak
Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#17
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28153727/cd40-agonist-converting-ctl-exhaustion-via-the-activation-of-the-mtorc1-pathway-enhances-pd-1-antagonist-action-in-rescuing-exhausted-ctls-in-chronic-infection
#18
Aizhang Xu, Rong Wang, Andrew Freywald, Kristoffor Stewart, Suresh Tikoo, Jianqing Xu, Changyu Zheng, Jim Xiang
Expansion of PD-1-expressing CD8(+) cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153342/calcium-nfat-transcriptional-signalling-in-t-cell-activation-and-t-cell-exhaustion
#19
REVIEW
Patrick G Hogan
A cornerstone of the adaptive immune response is the T cell receptor (TcR)-calcium-calcineurin signalling pathway leading to T cell activation. The 'nuclear factor of activated T cells' proteins NFAT1, NFAT2, and NFAT4 are transcription factors that promote expression of a panel of genes required for activation. It has become apparent that these same NFAT transcription factors underlie an alternative transcriptional program in T cells that serves to limit the immune response. This duality in NFAT transcriptional functions raises the possibility that NFAT transcriptional complexes could be targeted therapeutically to alter the relative strength of the effector and alternative transcriptional programs, thereby modulating immune responses...
January 28, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#20
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
1, 2017: Nature
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