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https://www.readbyqxmd.com/read/28742871/comprehensive-immune-profiling-reveals-substantial-immune-system-alterations-in-a-subset-of-patients-with-amyotrophic-lateral-sclerosis
#1
Michael P Gustafson, Nathan P Staff, Svetlana Bornschlegl, Greg W Butler, Mary L Maas, Mohamed Kazamel, Adeel Zubair, Dennis A Gastineau, Anthony J Windebank, Allan B Dietz
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a median lifespan of 2-3 years after diagnosis. There are few meaningful treatments that alter progression in this disease. Preclinical and clinical studies have demonstrated that neuroinflammation may play a key role in the progression rate of ALS. Despite this, there are no validated biomarkers of neuroinflammation for use in clinical practice or clinical trials. Biomarkers of neuroinflammation could improve patient management, provide new therapeutic targets, and possibly help stratify clinical trial selection and monitoring...
2017: PloS One
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#2
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741496/targeting-bcl-2-like-proteins-to-kill-cancer-cells
#3
REVIEW
Suzanne Cory, Andrew W Roberts, Peter M Colman, Jerry M Adams
Mutations that impair apoptosis contribute to cancer development and reduce the effectiveness of conventional anti-cancer therapies. These insights and understanding of how the B cell lymphoma (BCL)-2 protein family governs apoptosis have galvanized the search for a new class of cancer drugs that target its pro-survival members by mimicking their natural antagonists, the BCL-2 homology (BH)3-only proteins. Successful initial clinical trials of the BH3 mimetic venetoclax/ABT-199, specific for BCL-2, have led to its recent licensing for refractory chronic lymphocytic leukemia and to multiple ongoing trials for other malignancies...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741259/adoptive-transfer-of-autoimmune-splenic-dendritic-cells-to-lupus-prone-mice-triggers-a-b-lymphocyte-humoral-response
#4
Daniela Sauma, Natalia Crisóstomo, Camila Fuentes, María Alejandra Gleisner, Yessia Hidalgo, María José Fuenzalida, Mario Rosemblatt, María Rosa Bono
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by increased autoantibody production that leads to multiple tissue injuries. Dendritic cells (DCs) are important orchestrators of immune responses and key components in fine-tuning the balance between tolerance and immunity. However, their role in autoimmune disorders such as SLE remains uncertain. We analyzed the contribution of DCs in triggering SLE by adoptively transferring splenic DCs from aged autoimmune [NZB×NZW]F1 (BWF1) mice to young healthy BWF1 mice...
July 25, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28741237/cytotoxic-t-lymphocytes-and-cd4-epitope-mutations-in-the-pre-core-core-region-of-hepatitis-b-virus-in-chronic-hepatitis-b-carriers-in-northeast-iran
#5
Sareh Zhand, Alijan Tabarraei, Amineh Nazari, Abdolvahab Moradi
BACKGROUNDS: Hepatitis B virus (HBV) is vulnerable to many various mutations. Those within epitopes recognized by sensitized T cells may influence the re-emergence of the virus. This study was designed to investigate the mutation in immune epitope regions of HBV pre-core/core among chronic HBV patients of Golestan province, Northeast Iran. METHODS: In 120 chronic HBV carriers, HBV DNA was extracted from blood plasma samples and PCR was done using specific primers...
July 25, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28740663/evaluation-of-platelet-lymphocyte-ratio-and-90-day-mortality-in-patients-with-acute-exacerbation-of-chronic-obstructive-pulmonary-disease
#6
Praneel Kumar, Stephanie Law, Krishna B Sriram
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have high mortality and health care costs. The platelet to lymphocyte ratio (PLR) is a marker of inflammation and has been reported to be elevated in patients with AECOPD compared to stable state. In this study, we sought to evaluate the association of the PLR in patients with AECOPD with 90-day mortality. METHODS: We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD between January 2014 and July 2014...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28739115/a-recombinant-protein-of-salmonella-typhi-induces-humoral-and-cell-mediated-immune-responses-including-memory-responses
#7
Sayan Das, Rimi Chowdhury, Shubhamoy Ghosh, Santasabuj Das
Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever is a major public health problem in developing countries. While a permanent solution to the problem would require improved sanitation, food and water hygiene, controlling the infection by vaccination is urgently required due to the emergence of multidrug resistant strains in multiple countries. The currently licensed vaccines are moderately efficacious with limited applicability, and no recommended vaccines exist for younger children...
July 21, 2017: Vaccine
https://www.readbyqxmd.com/read/28738086/an-essential-ebv-latent-antigen-3c-binds-bcl6-for-targeted-degradation-and-cell-proliferation
#8
Yonggang Pei, Shuvomoy Banerjee, Hem Chandra Jha, Zhiguo Sun, Erle S Robertson
The latent EBV nuclear antigen 3C (EBNA3C) is required for transformation of primary human B lymphocytes. Most mature B-cell malignancies originate from malignant transformation of germinal center (GC) B-cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is Bcl6, a key regulator of this process. We now demonstrate that EBNA3C contributes to B-cell transformation by targeted degradation of Bcl6. We show that EBNA3C can physically associate with Bcl6...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#9
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#10
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28737722/induction-of-a-regulatory-phenotype-in-cd3-cd4-hla-dr-t-cells-after-allogeneic-mixed-lymphocyte-culture-indications-of-both-contact-dependent-and-independent-activation
#11
Anne Louise Schacht Revenfeld, Rikke Bæk, Malene Møller Jørgensen, Kim Varming, Allan Stensballe
Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#12
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737232/chlorinated-adenosine-analogue-induces-ampk-and-autophagy-in-chronic-lymphocytic-leukaemia-cells-during-therapy
#13
Christine M Stellrecht, Lisa S Chen, Mary L Ayres, Jennifer B Dennison, Shujun Shentu, Yuling Chen, Michael J Keating, William G Wierda, Varsha Gandhi
8-chloro-adenosine (8-Cl-Ado) is currently in phase-I clinical trials for acute myeloid leukaemia and chronic lymphocytic leukaemia (CLL). Previously, we demonstrated that treatment with 8-Cl-Ado leads to diminished ATP levels. We hypothesized that AMP-activated protein kinase (AMPK) signalling would be initiated in these cells, leading to induction of autophagy. AMPK activation and induction of autophagy were demonstrated during preclinical incubations in CLL cells with the analogues. Importantly, we extended similar observations in CLL lymphocytes during an 8-Cl-Ado phase-I trial...
July 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28736577/optimization-of-proximity-ligation-assay-pla-for-detection-of-protein-interactions-and-fusion-proteins-in-non-adherent-cells-application-to-pre-b-lymphocytes
#14
Lydie Debaize, Hélène Jakobczyk, Anne-Gaëlle Rio, Virginie Gandemer, Marie-Bérengère Troadec
BACKGROUND: Genetic abnormalities, including chromosomal translocations, are described for many hematological malignancies. From the clinical perspective, detection of chromosomal abnormalities is relevant not only for diagnostic and treatment purposes but also for prognostic risk assessment. From the translational research perspective, the identification of fusion proteins and protein interactions has allowed crucial breakthroughs in understanding the pathogenesis of malignancies and consequently major achievements in targeted therapy...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28736554/differential-requirements-for-src-family-kinases-in-syk-or-zap70-mediated-slp-76-phosphorylation-in-lymphocytes
#15
Frank Fasbender, Maren Claus, Sabine Wingert, Mina Sandusky, Carsten Watzl
In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28735348/analysis-of-the-cd8-t-cell-anti-hiv-activity-in-heterologous-cell-co-cultures-reveals-the-benefit-of-multiple-hla-class-i-matches
#16
M Scott Killian, Fernando Teque, Ramu Sudhagoni
CD8(+) T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4(+) T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8(+) T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4(+) T cells. Altogether, CD8(+) T cell anti-HIV activity was evaluated in more than 200 co-cultures...
July 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28733541/a-validated-transitional-and-translational-porcine-model-of-hepatocellular-carcinoma
#17
Kyle M Schachtschneider, Regina M Schwind, Kwame A Darfour-Oduro, Arun K De, Lauretta A Rund, Kuldeep Singh, Daniel R Principe, Grace Guzman, Charles E Ray, Howard Ozer, Ron C Gaba, Lawrence B Schook
Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733045/induction-of-live-cell-phagocytosis-by-a-specific-combination-of-inflammatory-stimuli
#18
Takamasa Ishidome, Takeshi Yoshida, Rikinari Hanayama
Conditions of severe hyper-inflammation can lead to uncontrolled activation of macrophages, and the ensuing phagocytosis of live cells. However, relationships between inflammatory stimuli and uncontrolled phagocytosis of live cells by macrophages are poorly understood. To identify mediators of this process, we established phagocytosis assays of live cells by stimulating macrophages with CpG DNA, interferon-γ, and anti-interleukin-10 receptor antibody. In this model, various cell surface receptors were upregulated on macrophages, and phagocytosis of live cells was induced in a Rac1-dependent manner...
July 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28732781/immunoglobulin-and-b-cell-disturbances-in-patients-with-chronic-idiopathic-neutropenia
#19
Irene Mavroudi, Aristides G Eliopoulos, Charalampos Pontikoglou, Katerina Pyrovolaki, Athina Damianaki, Helen Koutala, Maria I Zervou, Maria Ximeri, Semeli Mastrodemou, Peggy Kanellou, George N Goulielmos, Helen A Papadaki
Chronic idiopathic neutropenia (CIN) is a granulocytic disorder associated with presence of activated, myelosuppressive T-lymphocytes. In the present study we have evaluated constituents of humoral immunity in CIN patients (n=48) compared to healthy controls (n=52). CIN patients displayed lower serum IgG levels due to a reduction in IgG1, IgG3, IgG4 but not IgG2, lower IgA and increased IgM levels compared to controls. The proportion of CD19(+) cells did not differ between patients and controls; however the proportion of the naïve IgD(+)/CD27(-) B-cells was increased and the proportion of class-switched memory IgD(-)/CD27(+) B-cells was decreased in the patients...
July 18, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28732506/new-insights-into-blimp-1-in-t-lymphocytes-a-divergent-regulator-of-cell-destiny-and-effector-function
#20
REVIEW
Shin-Huei Fu, Li-Tzu Yeh, Chin-Chen Chu, B Lin-Ju Yen, Huey-Kang Sytwu
B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3(+) regulatory T cells with an effector phenotype...
July 21, 2017: Journal of Biomedical Science
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