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https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#1
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329310/immunologic-pathways-that-predict-mortality-in-hiv-infected-ugandans-initiating-art
#2
Sulggi Lee, Helen Byakwaga, Yap Boum, Tricia H Burdo, Kenneth C Williams, Michael M Lederman, Yong Huang, Russell P Tracy, Huyen Cao, Jessica E Haberer, Annet Kembabazi, David R Bangsberg, Jeffrey N Martin, Peter W Hunt
Plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated HIV disease in Ugandans compared to U.S.-based populations, Here, KT ratio, and T cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. Month 6 KT ratio (aHR=2.74), sCD14 (aHR=2.32), IL-6 (aHR=2.34), and D dimer (aHR=1.95) were associated with mortality occurring ≥6 months after ART initiation, KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings...
March 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#3
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329242/vaccination-induces-cd4-t-cell-mediated-mortality-during-staphylococcus-aureus-bacteremia
#4
Hatice Karauzum, Christian C Haudenschild, Ian N Moore, Mahta Mahmoudieh, Daniel L Barber, Sandip K Datta
Multiple candidate vaccines against Staphylococcus aureus infections have failed in clinical trials. Analysis of a recent prematurely halted vaccine trial revealed increased mortality among vaccine recipients who developed post-surgical S. aureus infection, emphasizing the potential for induction of detrimental immune responses and the need to better understand the requirements for protective immunity against S. aureus. These failures of single antigen vaccines have prompted ongoing development of multi-component vaccines to target the multitude of S...
February 21, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329211/therapeutic-vaccine-for-genital-herpes-simplex-virus-2-infection-findings-from-a-randomized-trial
#5
David I Bernstein, Anna Wald, Terri Warren, Kenneth Fife, Stephen Tyring, Patricia Lee, Nick Van Wagoner, Amalia Magaret, Jessica B Flechtner, Sybil Tasker, Jason Chan, Amy Morris, Seth Hetherington
Background.: Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2ΔTMR and ICP4.2, and Matrix-M2 adjuvant. Methods.: Persons with genital herpes were randomized into three dose cohorts to receive three intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swabs twice-daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and intervals after the last dose...
January 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329174/ccr7-deficiency-modulates-t-cell-response-and-increases-susceptibility-to-yersinia-pseudotuberculosis-infection
#6
Joern Pezoldt, Fabio Pisano, Wiebke Heine, Maria Pasztoi, Maik Rosenheinrich, Aaron M Nuss, Marina C Pils, Immo Prinz, Reinhold Förster, Jochen Huehn, Petra Dersch
Background: To successfully limit pathogen dissemination an immunological link between the entry tissue of the pathogen and the underlying secondary lymphoid organs (SLO) needs to be established to prime adaptive immune responses. Here, the prerequisite of CCR7 to mount host immune responses within SLOs during gastrointestinal Yersinia pseudotuberculosis infection to limit pathogen spread was investigated. Methods: Survival, bacterial dissemination, intestinal and systemic pathology of wild type (WT) and CCR7-/- mice were assessed and correlated to the presence of immune cell subsets and cytokine responses throughout the course of infection...
January 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329119/stratification-of-latent-tuberculosis-infection-by-cellular-immune-profiling
#7
Alice Halliday, Hilary Whitworth, Sherine Hermagild Kottoor, Umar Niazi, Sarah Menzies, Heinke Kunst, Samuel Bremang, Amarjit Badhan, Peter Beverley, Onn Min Kon, Ajit Lalvani
Background: Recently-acquired and remotely-acquired latent tuberculosis (TB) infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to active TB (ATB) in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures which differ between ATB and LTBI, to distinguish recently from remotely acquired LTBI. Methods: Fifty-nine individuals were recruited: ATB (n=20); recent LTBI (n=19); remote LTBI (n=20)...
February 28, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328807/associations-of-il-4-il-6-and-il-12-levels-in-peripheral-blood-with-lung-function-cellular-immune-function-and-quality-of-life-in-children-with-moderate-to-severe-asthma
#8
Ai-Hua Cui, Jing Zhao, Shu-Xiang Liu, Ying-Shuang Hao
BACKGROUND: Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. METHODS: A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328797/activation-senescence-and-inflammation-markers-in-hiv-patients-association-with-renal-function
#9
Alexandra Ozanne, Pierre Duffau, Frédéric-Antoine Dauchy, Claire Rigothier, Cécile Terrien, Estibaliz Lazaro, Charles Cazanave, Sylvie Lawson-Ayayi, Fabrice Bonnet, Patrick Blanco, Linda Wittkop, Isabelle Pellegrin
OBJECTIVES: To assess the association between immune-activation (IA), immune-senescence (IS), inflammation biomarkers and renal function measured by estimated glomerular function rate (eGFR) at inclusion and its evolution over a 3-years follow-up in HIV-infected patients with undetectable viral load. DESIGN: The CIADIS (Chronic Immune Activation anD Senescence) sub-study consecutively included patients between October 2011 and May 2013 enrolled in the ANRS CO3 Aquitaine observational cohort...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#10
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#11
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327819/cellular-immunodeficiency-related-to-chronic-dermatophytosis-in-a-patient-with-schistosoma-mansoni-infection-can-schistosomiasis-induce-immunodeficiency
#12
Maurício Domingues Ferreira, Anna Cristina Collaniere, Dalton Luís Bertolini, Noac Chuffi Barros, Dewton de Moraes Vasconcelos
Here, we describe a case of hepatosplenic schistosomiasis that progressed to widespread persistent dermatophytosis. Significant T and B lymphocytopenia was confirmed. T-cell deficit is associated with increased susceptibility to fungal infections of skin and mucous membranes. The accumulation of a large amount of blood cells in the spleen could have played a crucial role in the development of lymphocytopenia in the present case. Alternatively, the schistosomiasis-induced increase in prostaglandin E2 levels could have inhibited the production of interferon-γ, a cytokine fundamental to fungal resistance...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327618/the-transcriptional-repressor-hic1-regulates-intestinal-immune-homeostasis
#13
K Burrows, F Antignano, M Bramhall, A Chenery, S Scheer, V Korinek, T M Underhill, C Zaph
The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327518/myeloid-c-type-lectin-receptors-in-viral-recognition-and-antiviral-immunity
#14
REVIEW
João T Monteiro, Bernd Lepenies
Recognition of viral glycans by pattern recognition receptors (PRRs) in innate immunity contributes to antiviral immune responses. C-type lectin receptors (CLRs) are PRRs capable of sensing glycans present in viral pathogens to activate antiviral immune responses such as phagocytosis, antigen processing and presentation, and subsequent T cell activation. The ability of CLRs to elicit and shape adaptive immunity plays a critical role in the inhibition of viral spread within the host. However, certain viruses exploit CLRs for viral entry into host cells to avoid immune recognition...
March 22, 2017: Viruses
https://www.readbyqxmd.com/read/28327462/neurocognitive-dysfunction-in-hiv-infected-youth-investigating-the-relationship-with-immune-activation
#15
Allison Ross Eckard, Julia C Rosebush, Mary Ann O'Riordan, Chanda C Graves, Ashley Alexander, Anita K Grover, S Thera Lee, Jakob G Habib, Joshua H Ruff, Ann Chahroudi, Grace A McComsey
BACKGROUND: HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. METHODS: HIV-infected youth 8-26 years old on cART with virologic suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales...
March 22, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28327177/intestinal-t-lymphocyte-homing-is-associated-with-gastric-emptying-and-epithelial-barrier-function-in-critically-ill-a-prospective-observational-study
#16
Christian Greis, Zohal Rasuly, Rolf A Janosi, Lambros Kordelas, Dietrich W Beelen, Tobias Liebregts
BACKGROUND: Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS: We conducted a prospective observational study at two tertiary care medical ICUs...
March 22, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28326907/skin-sensitizers-in-cosmetics-and-beyond-potential-multiple-mechanisms-of-action-and-importance-of-t-cell-assays-for-in-vitro-screening
#17
Stanislav Vukmanović, Nakissa Sadrieh
Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity (DTH) reaction induced by repeated contact with sensitizers. The ability of a chemical to act as a sensitizer has most frequently been tested in animals. As the use of animals for these purposes is gradually and globally being phased out, there is a need for reliable in vitro surrogate assays. Currently proposed in vitro assays are designed to test four key events of the adverse outcome pathway (AOP) involving covalent modification of self-proteins by sensitizers (haptenation) and presentation of new antigens (hapten/carrier complexes) to the immune system...
March 22, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28326848/autologous-hematopoietic-stem-cells-for-refractory-crohn-s-disease
#18
C A DiNicola, A Zand, D W Hommes
Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28326672/bk-polyomavirus-specific-9mer-cd8-t-cell-responses-correlate-with-clearance-of-bk-viremia-in-kidney-transplant-recipients-first-report-from-the-swiss-transplant-cohort-study-stcs
#19
Céline Leboeuf, Sabrina Wilk, Rita Achermann, Isabelle Binet, Dela Golshayan, Karin Hadaya, Cedric Hirzel, Matthias Hoffmann, Uyen Huynh-Do, Michael T Koller, Oriol Manuel, Nicolas J Mueller, Thomas F Mueller, Stefan Schaub, Christian van Delden, Fabian H Weissbach, Hans H Hirsch
BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Since antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and PBMCs at T0, T6, and T12 months post-transplant from 28 viremic KT patients and 68 non-viremic controls matched for the transplantation period. BKPyV-IgG seroprevalence was comparable between cases (89...
March 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28326600/prognostic-significance-of-tumour-infiltrating-b-lymphocytes-in-breast-ductal-carcinoma-in-situ
#20
I Miligy, P Mohan, A Gaber, M A Aleskandarany, C C Nolan, M Diez-Rodriguez, A Mukherjee, C Chapman, I O Ellis, A R Green, E A Rakha
BACKGROUND: Tumour infiltrating lymphocytes are an important component of the immune response to cancer and have a prognostic value in breast cancer. Although several studies have investigated the role of T-lymphocytes in breast cancer, the role of B lymphocytes (TIL-Bs) in Ductal carcinoma in situ (DCIS), remains uncertain. This study aimed to assess the role of TIL-Bs in DCIS. METHODS: 80 DCIS cases (36 pure DCIS and 44 mixed with invasive cancer) were immunohistochemically stained for B lineage markers CD19, CD20 and the plasma cell marker CD138...
March 22, 2017: Histopathology
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