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Exhausted T cell

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https://www.readbyqxmd.com/read/29236302/recovery-of-hepatitis-c-specific-t-cell-responses-after-rituximab-therapy-in-hepatitis-c-mixed-cryoglobulinemic-vasculitis
#1
Poonam Mathur, Benjamin Emmanuel, Michael Sneller, Xiaozhen Zhang, Bhawna Poonia, Shyamasundaran Kottilil
BACKGROUND & AIMS: Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function. METHODS: Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375mg/m2 ) and variables were measured 6 months after therapy...
December 13, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29234685/local-and-systemic-cd4-t-cell-exhaustion-reverses-with-clinical-resolution-of-pulmonary-sarcoidosis
#2
Charlene Hawkins, Guzel Shaginurova, D Auriel Shelton, Jose D Herazo-Maya, Kyra A Oswald-Richter, Joseph E Rotsinger, Anjuli Young, Lindsay J Celada, Naftali Kaminski, Carla Sevin, Wonder P Drake
Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#3
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29232209/recent-progress-in-understanding-hiv-reservoirs
#4
Hsiao-Hsuan Kuo, Mathias Lichterfeld
PURPOSE OF REVIEW: Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. RECENT FINDINGS: Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs...
December 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29224832/the-pathogenesis-of-pulmonary-sarcoidosis-and-implications-for-treatment
#5
REVIEW
Karen C Patterson, Edward S Chen
Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a heterogeneous group of patients with a wide range of clinical features and associated outcomes. The distinction between isolated thoracic lymphadenopathy and pulmonary involvement matters. Morbidity is often higher, and long-term outcomes are worse for the latter. While inflammatory infiltrates in pulmonary sarcoidosis may resolve, persistent disease activity is common and can result in lung fibrosis. Given the distinct clinical features and natural history of pulmonary sarcoidosis, its pathogenesis may differ in important ways from other sarcoidosis manifestations...
December 7, 2017: Chest
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#6
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
PURPOSE: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing co-inhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. EXPERIMENTAL DESIGN: Surface expression of 9 co-inhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#7
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29213079/human-cd26high-t-cells-elicit-tumor-immunity-against-multiple-malignancies-via-enhanced-migration-and-persistence
#8
Stefanie R Bailey, Michelle H Nelson, Kinga Majchrzak, Jacob S Bowers, Megan M Wyatt, Aubrey S Smith, Lillian R Neal, Keisuke Shirai, Carmine Carpenito, Carl H June, Michael J Zilliox, Chrystal M Paulos
CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29211494/exhaustion-of-airway-basal-progenitor-cells-in-early-and-established-copd
#9
Moumita Ghosh, York E Miller, Ichiro Nakachi, Jennifer B Kwon, Anna E Barón, Alexandra E Brantley, Daniel T Merrick, Wilbur A Franklin, Robert L Keith, R William Vandivier
RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, pre-diagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience, because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired...
December 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29198314/t-cell-resistance-to-activation-by-dendritic-cells-requires-long-term-culture-in-simulated-microgravity
#10
Jillian H Bradley, Rachel Stein, Brad Randolph, Emily Molina, Jennifer P Arnold, Randal K Gregg
Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines...
November 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29197679/recipient-t-cell-exhaustion-and-successful-adoptive-transfer-of-haploidentical-natural-killer-cells
#11
Robin L Williams, Sarah Cooley, Veronika Bachanova, Bruce R Blazar, Daniel J Weisdorf, Jeffrey S Miller, Michael R Verneris
NK cells mediate surveillance for malignancy. In some chemotherapy refractory myeloid leukemia patients, adoptive transfer of NK cells from haploidentical donors can induce remission. We have previously shown that remission induction is linked to NK persistence at D+14, but the factors influencing NK cell persistence are unknown. To address this question, patient samples from a phase I trial of NCI IL-15 in whom either did or did not show NK cell expansion were compared to healthy donor controls. Prior to lymphodepleting chemotherapy, high absolute CD3+ count was predictive of patients who failed to expand their haplo-NK cell graft...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29196449/sustained-t-follicular-helper-cell-response-is-essential-for-control-of-chronic-viral-infection
#12
Ute Greczmiel, Nike Julia Kräutler, Alessandro Pedrioli, Ilka Bartsch, Paola Agnellini, Gregor Bedenikovic, James Harker, Kirsten Richter, Annette Oxenius
During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5+ T follicular helper cell (TFH) lineage. Whether these TFH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29195371/cat-act-a-new-highly-versatile-x-ray-spectroscopy-beamline-for-catalysis-and-radionuclide-science-at-the-kit-synchrotron-light-facility-anka
#13
A Zimina, K Dardenne, M A Denecke, D E Doronkin, E Huttel, H Lichtenberg, S Mangold, T Pruessmann, J Rothe, Th Spangenberg, R Steininger, T Vitova, H Geckeis, J-D Grunwaldt
CAT-ACT-the hard X-ray beamline for CATalysis and ACTinide/radionuclide research at the KIT synchrotron radiation facility ANKA-is dedicated to X-ray spectroscopy, including "flux hungry" photon-in/photon-out and correlative techniques and combines state-of-the-art optics with a unique infrastructure for radionuclide and catalysis research. Measurements can be performed at photon energies varying between 3.4 keV and 55 keV, thus encompassing the actinide M- and L-edge or potassium K-edge up to the K-edges of the lanthanide series such as cerium...
November 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/29195073/epigenetic-therapy-ties-myc-depletion-to-reversing-immune-evasion-and-treating-lung-cancer
#14
Michael J Topper, Michelle Vaz, Katherine B Chiappinelli, Christina E DeStefano Shields, Noushin Niknafs, Ray-Whay Chiu Yen, Alyssa Wenzel, Jessica Hicks, Matthew Ballew, Meredith Stone, Phuoc T Tran, Cynthia A Zahnow, Matthew D Hellmann, Valsamo Anagnostou, Pamela L Strissel, Reiner Strick, Victor E Velculescu, Stephen B Baylin
Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29188192/unlocking-the-epigenetic-code-of-t-cell-exhaustion
#15
Jiazhu Wu, Huidong Shi
No abstract text is available yet for this article.
March 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/29185390/modulation-of-antitumor-immunity-with-histone-deacetylase-inhibitors
#16
Tyler R McCaw, Troy D Randall, Andres Forero, Donald J Buchsbaum
Histone deacetylase inhibitors possess a broad array of antitumor activities; however, their net impact on the evolving antitumor immune response is highly dependent on the inhibitors used and the histone deacetylases they target. Herein, we sequentially focus on each stage of the antitumor immune response - from dendritic cell activation and migration, antigen uptake and presentation, T-cell activation and differentiation and the enactment of antitumor effector functions within the tumor microenvironment. In particular, we will discuss how various inhibitors have different effects depending on cellular activation, experimental design and specific histone deacetylases being targeted - and how these changes impact the outcome of an antitumor immune response...
December 2017: Immunotherapy
https://www.readbyqxmd.com/read/29184980/blockage-of-the-nlrp3-inflammasome-by-mcc950-improves-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#17
Lei Chen, Cong-Fa Huang, Yi-Cun Li, Wei-Wei Deng, Liang Mao, Lei Wu, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues...
November 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29176992/immunosenescence-in-persons-with-spinal-cord-injury-in-relation-to-urinary-tract-infections-a-cross-sectional-study
#18
David Pavlicek, Jörg Krebs, Simona Capossela, Alessandro Bertolo, Britta Engelhardt, Jürgen Pannek, Jivko Stoyanov
Background: Individuals with a spinal cord injury (SCI), despite specialized rehabilitation and good health care, have a reduced life expectancy. Infectious diseases, such as pneumonias, infected pressure sores and urinary tract infections (UTI) have been identified as the leading causes of mortality. We hypothesise that a premature onset of immune frailty occurs in SCI, possibly caused also by recurrent urinary tract infections.A cross sectional study was performed comparing blood and urine samples between able bodied controls (n = 84) and persons with spinal cord injury (n = 85)...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/29176744/crucial-role-of-mir-31-in-induction-of-cd8-t-cell-exhaustion-and-reinforcement-of-type-1-interferon-signaling
#19
Lin Ying Li, Inkyu Hwang
No abstract text is available yet for this article.
November 27, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29167392/tcr-engagement-negatively-affects-cd8-but-not-cd4-car-t-cell-expansion-and-leukemic-clearance
#20
Yinmeng Yang, M Eric Kohler, Christopher D Chien, Christopher T Sauter, Elad Jacoby, Chunhua Yan, Ying Hu, Kelsey Wanhainen, Haiying Qin, Terry J Fry
Chimeric antigen receptor (CAR)-expressing T cells induce durable remissions in patients with relapsed/refractory B cell malignancies. CARs are synthetic constructs that, when introduced into mature T cells, confer a second, non-major histocompatibility complex-restricted specificity in addition to the endogenous T cell receptor (TCR). The implications of TCR activation on CAR T cell efficacy has not been well defined. Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre-B cell acute lymphoblastic leukemia in which the CAR is introduced into T cells with known TCR specificity, we demonstrate loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when TCR antigen is present...
November 22, 2017: Science Translational Medicine
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