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https://www.readbyqxmd.com/read/28334641/humanized-mouse-model-for-assessing-the-human-immune-response-to-xenogeneic-and-allogeneic-decellularized-biomaterials
#1
Raymond M Wang, Todd D Johnson, Jingjin He, Zhili Rong, Michelle Wong, Vishal Nigam, Atta Behfar, Yang Xu, Karen L Christman
Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared...
March 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#2
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#3
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28333137/the-mtor-signal-regulates-myeloid-derived-suppressor-cells-differentiation-and-immunosuppressive-function-in-acute-kidney-injury
#4
Chao Zhang, Shuo Wang, Jiawei Li, Weitao Zhang, Long Zheng, Cheng Yang, Tongyu Zhu, Ruiming Rong
The mammalian target of rapamycin (mTOR) signal controls innate and adaptive immune response in multiple immunoregulatory contexts. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells of potent immunosuppressive capacity. In this study, we aimed to investigate the role of MDSCs in the protection of acute kidney injury (AKI) and the regulation of mTOR signal on MDSC's protective role in this context. In mice AKI model, rapamycin administration was associated with improved renal function, restored histological damage and decreased CD4(+) and CD8(+) T-cell infiltration in kidney tissue...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332288/tetrandrine-an-agonist-of-aryl-hydrocarbon-receptor-reciprocally-modulates-the-activities-of-stat3-and-stat5-to-suppress-th17-cell-differentiation
#5
Xusheng Yuan, Yannong Dou, Xin Wu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid constituent of the root of Stephania tetrandra S. Moore, was previously shown to suppress the differentiation of T helper 17 (Th17) cells and consequently ameliorate the collagen-induced arthritis (CIA) in mice by activating the aryl hydrocarbon receptor (AhR), but its underlying mechanism is incompletely understood. Here, we investigated how tetrandrine suppressed Th17 cell differentiation through the AhR pathway. The naïve CD4(+) T cells were stimulated with anti-CD3/CD28 for 72 hrs in the presence or absence of tetrandrine under the Th17-polarizing condition...
March 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28332270/changes-in-elevated-cholesterol-in-the-era-of-tenofovir-in-south-africa-risk-factors-clinical-management-and-outcomes
#6
L Jamieson, D Evans, A T Brennan, F Moyo, D Spencer, K Mahomed, M Maskew, L Long, S Rosen, M P Fox
OBJECTIVES: Antiretroviral therapy (ART) has been associated with unfavourable lipid profile changes and increased risk of cardiovascular disease (CVD). With a growing population on ART in South Africa, there has been concern about the increase in noncommunicable diseases such as CVD. We determined risk factors associated with increased total cholesterol (TC) in a large cohort on ART and describe the clinical management thereof. METHODS: We conducted an observational cohort study of ART-naïve adults initiating standard first-line ART in a large urban clinic in Johannesburg, South Africa...
March 23, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28331526/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#7
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28331303/soluble-common-gamma-chain-exacerbates-copd-progress-through-the-regulation-of-inflammatory-t-cell-response-in-mice
#8
Byunghyuk Lee, Eunhee Ko, Jiyeon Lee, Yuna Jo, Hyunju Hwang, Tae Sik Goh, Myungsoo Joo, Changwan Hong
Cigarette smoking (CS) is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc) has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE) mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN) is systemically reduced in the CSE group...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28331190/natural-killer-cell-activation-contributes-to-hepatitis-b-viral-control-in-a-mouse-model
#9
Shiwen Tong, Guangze Liu, Minghong Li, Xiumei Li, Qian Liu, Hong Peng, Shiying Li, Hong Ren, Wenwei Yin
The roles of CD4 + T cells and CD8 + T cells in hepatitis B virus (HBV) infection have been well documented. However, the role of innate immunity in HBV infection remains obscure. Here we examined the effect of activation of innate immunity by polyinosinic: polycytidylic acid (PolyI:C) on HBV infection. A chronic HBV replication mouse model was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. We found that HBV did not seem to induce an active NK-cell response in the mouse model...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331180/ccr5-promoter-activity-correlates-with-hiv-disease-progression-by-regulating-ccr5-cell-surface-expression-and-cd4-t-cell-apoptosis
#10
Anjali Joshi, Erin B Punke, Melina Sedano, Bethany Beauchamp, Rima Patel, Cassady Hossenlopp, Ogechika K Alozie, Jayanta Gupta, Debabrata Mukherjee, Himanshu Garg
CCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathological features like immune activation and CD4+ T cell apoptosis in HIV patients. CCR5 promoter haplotype HHC was significantly associated with higher CD4 counts in patients. The relative promoter activity (RPA) of each haplotype was determined in vitro and combined promoter activity based on both alleles (CRPA) was assigned to each patients...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331090/hili-inhibits-hiv-replication-in-activated-t-cells
#11
B Matija Peterlin, Pingyang Liu, Xiaoyun Wang, Daniele Cary, Wei Shao, Marie Leoz, Tian Hong, Tao Pan, Koh Fujinaga
Piwil proteins restrict the replication of mobile genetic elements in the germline. They are also expressed in many transformed cell lines. In this report, we discovered that the human piwil 2 (hili) can also inhibit HIV replication, especially in activated CD4+ T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express hili, it was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of hili increased levels of viral proteins and new viral particles...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331088/bst-2-expression-modulates-small-cd4-mimetic-sensitization-of-hiv-1-infected-cells-to-adcc
#12
Jonathan Richard, Jérémie Prévost, Benjamin von Bredow, Shilei Ding, Nathalie Brassard, Halima Medjahed, Mathieu Coutu, Bruno Melillo, Frédéric Bibollet-Ruche, Beatrice H Hahn, Daniel E Kaufmann, Amos B Smith, Joseph Sodroski, Daniel Sauter, Frank Kirchhoff, Katrina Gee, Stuart J Neil, David T Evans, Andrés Finzi
Antibodies recognizing conserved CD4-induced (CD4i) epitopes on HIV-1 Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV+ sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4-mimetics (CD4mc) which are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331083/maintenance-of-the-hiv-reservoir-is-antagonized-by-selective-bcl2-inhibition
#13
Nathan W Cummins, Amy M Sainski-Nguyen, Sekar Natesampillai, Fatma Aboulnasr, Scott Kaufmann, Andrew D Badley
Decay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV infected cells. This expansion reflects homeostatic proliferation of infected cells by IL-7 or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate BAK to induce apoptosis of infected cells...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#14
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330898/antigen-presenting-human-%C3%AE-%C3%AE-t-cells-promote-intestinal-cd4-t-cell-expression-of-il-22-and-mucosal-release-of-calprotectin
#15
Christopher J Tyler, Neil E McCarthy, James O Lindsay, Andrew J Stagg, Bernhard Moser, Matthias Eberl
The cytokine IL-22 plays a critical role in mucosal barrier defense, but the mechanisms that promote IL-22 expression in the human intestine remain poorly understood. As human microbe-responsive Vγ9/Vδ2 T cells are abundant in the gut and recognize microbiota-associated metabolites, we assessed their potential to induce IL-22 expression by intestinal CD4(+) T cells. Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4(+) T cells obtained from human blood or the colon...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330896/cell-specific-variation-in-e-selectin-ligand-expression-among-human-peripheral-blood-mononuclear-cells-implications-for-immunosurveillance-and-pathobiology
#16
Mariana Silva, Ronald Kam Fai Fung, Conor Brian Donnelly, Paula Alexandra Videira, Robert Sackstein
Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and Western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28329770/antigen-presentation-profiling-reveals-recognition-of-lymphoma-immunoglobulin-neoantigens
#17
Michael S Khodadoust, Niclas Olsson, Lisa E Wagar, Ole A W Haabeth, Binbin Chen, Kavya Swaminathan, Keith Rawson, Chih Long Liu, David Steiner, Peder Lund, Samhita Rao, Lichao Zhang, Caleb Marceau, Henning Stehr, Aaron M Newman, Debra K Czerwinski, Victoria E H Carlton, Martin Moorhead, Malek Faham, Holbrook E Kohrt, Jan Carette, Michael R Green, Mark M Davis, Ronald Levy, Joshua E Elias, Ash A Alizadeh
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28329768/corrigendum-cell-death-by-pyroptosis-drives-cd4-t-cell-depletion-in-hiv-1-infection
#18
Gilad Doitsh, Nicole L K Galloway, Xin Geng, Zhiyuan Yang, Kathryn M Monroe, Orlando Zepeda, Peter W Hunt, Hiroyu Hatano, Stefanie Sowinski, Isa Muñoz-Arias, Warner C Greene
No abstract text is available yet for this article.
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#19
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329608/atypical-lymphoproliferative-disorder-clinical-and-pathological-features
#20
Kelly Wilmas, Madeleine Duvic, Yasuhiro Oki
Definitive diagnosis of cutaneous lymphoproliferative disorders is one of the most challenging issues in dermatopathology owing to the broad spectrum of clinical and histopathological presentations. We report a case of a 73-year-old woman who presented with a single, asymptomatic plaque limited to her left collarbone. This was followed by the appearance of several plaques and patches in addition to a tumor. Her initial biopsy suggested a CD4/CD8 double negative mycosis fungoides (MF). However, the rapidly progressive course of her disease is worrisome for peripheral T-cell lymphomas-not otherwise specified (PTCL-NOS)...
September 15, 2016: Dermatology Online Journal
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