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Felicia C Chow, Michael R Wilson, Kunling Wu, Ronald J Ellis, Ronald J Bosch, Benjamin P Linas
OBJECTIVE: To investigate the incidence of first-ever stroke/transient ischemic attack (TIA) and associated risk factors in a cohort of persons living with HIV infection (PLWH). DESIGN: Observational cohort study METHODS:: We determined incidence rates of first-ever stroke/TIA in PLWH after ART initiation from the AIDS Clinical Trials Group ALLRT cohort and its parent trials. Poisson regression models evaluated baseline and time-varying covariates as risk factors for stroke/TIA...
March 15, 2018: AIDS
Elena García-Payá, Marta Fernández, Sergio Padilla, José A García, Catalina Robledano, Victoria Ortiz DE LA Tabla, Félix Gutiérrez, Mar Masiá
OBJECTIVE: The protective effect of ART has not yet been definitively established in men who have sex with men (MSM). We aimed to characterize the factors associated with persistent HIV-1 RNA rectal shedding. METHODS: Prospective study including virologically-suppressed MSM from an HIV cohort. High-resolution anoscopy (HRA) was performed for screening of anal dysplasia, and rectal sampling for HIV-1 RNA quantification and sexually-transmitted infections (STIs) investigation through multiplex PCR...
March 15, 2018: AIDS
Agata Schramm-Luc, Jolanta Schramm, Mateusz Siedliński, Tomasz J Guzik, Bogdan Batko
Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TNF) α inhibitors in ankylosing spondylitis (AS) patients; therefore, the aim of the study was to determine age-related differences in cellular functions, which can predict the response. High disease activity AS patients were treated with TNFα inhibitors for 12 weeks. Based on the percentage of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement, patients were divided into responding or non-responding groups...
March 15, 2018: Clinical Rheumatology
Rob R H van den Brom, Kornelis S M van der Geest, Elisabeth Brouwer, Geke A P Hospers, Annemieke M H Boots
The biological behavior of melanoma is unfavorable in the elderly when compared to young subjects. We hypothesized that differences in T-cell responses might underlie the distinct behavior of melanoma in young and old melanoma patients. Therefore, we investigated the circulating T-cell compartment of 34 patients with metastatic melanoma and 42 controls, which were classified as either young or old. Absolute numbers of CD4+ T cells were decreased in young and old melanoma patients when compared to the age-matched control groups...
March 15, 2018: Cancer Immunology, Immunotherapy: CII
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Mariona Camps-Bossacoma, Francisco J Pérez-Cano, Àngels Franch, Margarida Castell
Background: A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties. Objectives: This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition...
March 1, 2018: Journal of Nutrition
Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Jason T C Lee, Iryna Shanina, Yung Ning Chu, Marc S Horwitz, James D Johnson
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14...
March 15, 2018: Scientific Reports
Michael D Oberst, Catherine Auge, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly McGlinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke de Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew Weinberg, Scott A Hammond
Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells...
March 15, 2018: Molecular Cancer Therapeutics
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
Marliane Batista Campos, Luciana Vieira do Rêgo Lima, Ana Carolina Stocco de Lima, Thiago Vasconcelos Dos Santos, Patrícia Karla Santos Ramos, Claudia Maria de Castro Gomes, Fernando Tobias Silveira
Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L...
2018: PloS One
Weiping Cao, Margarita Mishina, Samuel Amoah, Wadzanai P Mboko, Caitlin Bohannon, James McCoy, Suresh K Mittal, Shivaprakash Gangappa, Suryaprakash Sambhara
Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI® , and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model...
November 2018: Drug Delivery
Zhe Du, Shujun Wang, Bing Yue, Ying Wang, You Wang
T-cells, second only to macrophages, are often considered as the potential cells involved in debris-related failure of arthroplasty. Here, we assessed the effects of particulate wear debris on T-cells and inflammatory reactions. Blood samples from 25 donors were incubated with polyether-ether-ketone (PEEK) and cobalt-chromium-molybdenum (CoCrMo) particles generated by custom cryo-milling and pulverization. The T-cell phenotypes were assessed using immunostaining and flow cytometry. For the in vivo study, 0...
February 16, 2018: Oncotarget
Antonella Mancusi, Sara Piccinelli, Andrea Velardi, Antonio Pierini
FoxP3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that can suppress proliferation and effector functions of T cells, B cells, NK cells, and antigen-presenting cells. Treg deficiency causes dramatic immunologic disease in both animal models and humans. As they are capable to suppress the function and the proliferation of conventional CD4+ and CD8+ T cells, Treg-based cell therapies are under evaluation for the treatment of various autoimmune diseases and are currently employed to prevent graft-versus-host disease (GvHD) in clinical trials of hematopoietic stem cell transplantation...
2018: Frontiers in Immunology
Wendy E Whatney, Neel R Gandhi, Cecilia S Lindestam Arlehamn, Azhar Nizam, Hao Wu, Melanie J Quezada, Angela Campbell, Salim Allana, Mbuyi Madeleine Kabongo, Jeremiah Khayumbi, Benson Muchiri, Joshua Ongalo, Joan Tonui, Loren E Sasser, Tawania J Fergus, Gregory Sadat Ouma, Samuel Gurrion Ouma, Allison A Beck, Mark J Mulligan, Alawode Oladele, Deepak Kaushal, Kevin P Cain, Lance Waller, Henry M Blumberg, John D Altman, Joel D Ernst, Jyothi Rengarajan, Cheryl L Day
Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis -specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sai Majji, Wathsala Wijayalath, Soumya Shashikumar, Teodor D Brumeanu, Sofia Casares
BACKGROUND: Human-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life cycle of Plasmodium falciparum. Herein, the DRAGA mice were investigated for immune responses following immunization with live P. falciparum sporozoites under chloroquine chemoprophylaxis (CPS-CQ), an immunization approach that showed in human trials to confer pre-erythrocytic immunity...
March 14, 2018: Malaria Journal
T Wang, M Remberger, U Axdorph Nygell, M Sundin, A Björklund, J Mattsson, M Uhlin, E Watz
BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival...
March 13, 2018: Transfusion
Christian D Fankhauser, Peter J Schüffler, Silke Gillessen, Aurelius Omlin, Niels J Rupp, Jan H Rueschoff, Thomas Hermanns, Cedric Poyet, Tullio Sulser, Holger Moch, Peter J Wild
Background: We aimed to analyze the frequency and distribution of PD-L1 expression in specimens from prostate cancer (PC) patients using two different anti-PD-L1 antibodies (E1L3N, SP263). Materials and Methods: PD-L1 immunohistochemistry was performed in a tissue microarray consisting of 82 castration-resistant prostate cancer (CRPC) specimens, 70 benign prostate hyperplasia (BPH) specimens, 96 localized PC cases, and 3 PC cell lines, using two different antibodies (clones E1L3N, and SP263)...
February 13, 2018: Oncotarget
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