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https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#1
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097812/monitoring-immune-response-after-allogeneic-transplantation-of-mesenchymal-stem-cells-for-osteochondral-repair
#2
Elhussein Elbadry Mahmoud, Tanaka Yuka, Naosuke Kamei, Yohei Harada, Hideki Ohdan, Adachi Nobuo, Mitsuo Ochi
The aim of this study was to investigate safety of using allogeneic magnetically labeled mesenchymal stem cells (m-MSCs) to ameliorate osteochondral repair as well as autologous one, with immune surveillance using a mixed lymphocyte reaction (MLR) assay. Twenty knees of Japanese white rabbits were randomly divided into two groups: the control (autologous) group, the transplantation of 2 × 10(5)  m-MSCs and the experimental (allogeneic) group, transplantation of 2 × 10(5)  m-MSCs from Dutch rabbit was performed, with exposure to an external magnetic device for 10 minutes, then rabbits were euthanized after 12 weeks...
January 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#3
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#4
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28097226/ifitm1-targets-hiv-1-latently-infected-cells-for-antibody-dependent-cytolysis
#5
Rui André Saraiva Raposo, Miguel de Mulder Rougvie, Dominic Paquin-Proulx, Phillip M Brailey, Vinicius D Cabido, Paul M Zdinak, Allison S Thomas, Szu-Han Huang, Greta A Beckerle, Richard B Jones, Douglas F Nixon
HIV-1 persistence in latent reservoirs during antiretroviral therapy (ART) is the main obstacle to virus eradication. To date, there is no marker that adequately identifies latently infected CD4(+) T cells in vivo. Using a well-established ex vivo model, we generated latently infected CD4(+) T cells and identified interferon-induced transmembrane protein 1 (IFITM1), a transmembrane antiviral factor, as being overexpressed in latently infected cells. By targeting IFITM1, we showed the efficient and specific killing of a latently infected cell line and CD4(+) T cells from ART-suppressed patients through antibody-dependent cytolysis...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28097068/hepatic-fibrosis-and-factors-associated-with-liver-stiffness-in-hiv-mono-infected-individuals
#6
Mihály Sulyok, Tamás Ferenci, Mihály Makara, Gábor Horváth, János Szlávik, Zsófia Rupnik, Luca Kormos, Zsuzsanna Gerlei, Zita Sulyok, István Vályi-Nagy
BACKGROUND: Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. METHODS: We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary...
2017: PeerJ
https://www.readbyqxmd.com/read/28097000/biased-small-molecule-ligands-for-selective-inhibition-of-hiv-1-cell-entry-via-ccr5
#7
Christian Berg, Katja Spiess, Hans R Lüttichau, Mette M Rosenkilde
Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096659/effects-of-multiple-dose-ponesimod-a-selective-s1p1-receptor-modulator-on-lymphocyte-subsets-in-healthy-humans
#8
Stipo Jurcevic, Pierre-Eric Juif, Colleen Hamid, Roseanna Greenlaw, Daniele D'Ambrosio, Jasper Dingemanse
This study investigated the effects of ponesimod, a selective S1P1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3:1). The overall change from baseline in lymphocyte count was -1,292±340×10(6) cells/L and 275±486×10(6) cells/L in ponesimod- and placebo-treated subjects, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28096525/toll-like-receptor-4-signaling-in-high-mobility-group-box-1-protein-1-mediated-the-suppression-of-regulatory-t-cells
#9
Chunyan Luo, Huiting Liu, Hu Wang, Jiajun Wang
BACKGROUND Treg cells play a central role in the suppression of immune response, and their suppressive capacity can be modulated by toll-like receptor (TLR) ligands. However, the detailed pathway of TLR ligand modulation is still unknown. The present study aimed to evaluate the effect of the high mobility group box-1 protein 1 (HMGB1) and lipopolysaccharide (LPS) on Treg cells through TLR4 signaling. MATERIAL AND METHODS Treg cells were purified from healthy human peripheral blood mononuclear cells (PBMCs) by magnetic-bead activity cell sorting (MACS), blocked by anti-TLR4 monoclonal antibody, and then incubated with different concentration of LPS or HMGB1...
January 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28096506/targeting-tnfr2-an-immune-checkpoint-stimulator-and-oncoprotein-is-a-promising-treatment-for-cancer
#10
REVIEW
Xin Chen, Joost J Oppenheim
Tumor necrosis factor receptor 2 (TNFR2) is expressed both by some cancer cells and by tumor-infiltrating immunosuppressive CD4(+)FoxP3(+) regulatory T cells (Tregs). TNFR2 stimulates the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses, and promotes cancer cell survival and tumor growth. In this issue of Science Signaling, Torrey et al found that dominant antagonistic antibodies against human TNFR2 may be a potential therapy for ovarian cancer patients by simultaneously suppressing Treg activity and inducing the death of the cancer cells...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096489/induced-packaging-of-cellular-micrornas-into-hiv-1-virions-can-inhibit-infectivity
#11
Hal P Bogerd, Edward M Kennedy, Adam W Whisnant, Bryan R Cullen
: Analysis of the incorporation of cellular microRNAs (miRNAs) into highly purified HIV-1 virions revealed that this largely, but not entirely, mirrored the level of miRNA expression in the producer CD4(+) T cells. Specifically, of the 58 cellular miRNAs detected at significant levels in the producer cells, only 5 were found in virions at a level 2- to 4-fold higher than that predicted on the basis of random cytoplasmic sampling. Of note, these included two miRNAs, miR-155 and miR-92a, that were reported previously to at least weakly bind HIV-1 transcripts...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#12
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#13
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096232/pr-957-a-selective-inhibitor-of-immunoproteasome-subunit-low-mw-polypeptide-7-attenuates-experimental-autoimmune-neuritis-by-suppressing-th17-cell-differentiation-and-regulating-cytokine-production
#14
Haijie Liu, Chunxiao Wan, Yanan Ding, Ranran Han, Yating He, Jinting Xiao, Junwei Hao
Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28095920/accuracy-of-who-immunological-criteria-in-identifying-virological-failure-among-hiv-infected-adults-on-first-line-antiretroviral-therapy-in-mwanza-north-western-tanzania
#15
Daniel W Gunda, Benson R Kidenya, Stephen E Mshana, Semvua B Kilonzo, Bonaventura C T Mpondo
BACKGROUND: Optimal HIV treatment monitoring remains a big challenge in resource limited settings. Guidelines recommend the use of clinical and immunological criteria in resource limited settings due to unavailability of viral load monitoring; however their utility is questionable. This study aimed at assessing the accuracy of immunological criteria in detecting treatment failure among HIV infected Tanzanian adults receiving first line ART. METHODS: A clinic based cross sectional study was conducted between February and July 2011 at Bugando Medical centre (BMC) HIV care and treatment clinic (CTC) involving HIV infected patients aged 18 years and above, receiving first line ART; followed up for at least 1 year...
January 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28095797/cocaine-crack-use-is-not-associated-with-fibrosis-progression-measured-by-ast-to-platelet-ratio-index-in-hiv-hcv-co-infected-patients-a-cohort-study
#16
Valérie Martel-Laferrière, Roy Nitulescu, Joseph Cox, Curtis Cooper, Mark Tyndall, Danielle Rouleau, Sharon Walmsley, Leo Wong, Marina B Klein
BACKGROUND: Cocaine and crack use has been associated with HIV and HCV infections, but its consequences on HCV progression have not been well established. We analyzed the impact of cocaine/crack use on liver fibrosis progression in a cohort of HIV-HCV co-infected patients. METHODS: A Canadian multicenter prospective cohort study followed 1238 HIV-HCV co-infected persons every 6 months between 2003 and 2013. Data were analyzed from 573 patients with positive HCV RNA, not on HCV treatment, without significant liver fibrosis (AST-to-Platelet Ratio Index (APRI) <1...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28095504/cytoplasmic-localization-of-htlv-1-hbz-protein-a-biomarker-of-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp
#17
Marco Baratella, Greta Forlani, Goutham U Raval, Alessandra Tedeschi, Olivier Gout, Antoine Gessain, Giovanna Tosi, Roberto S Accolla
HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP...
January 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28095439/intracranial-injection-of-dengue-virus-induces-interferon-stimulated-genes-and-cd8-t-cell-infiltration-by-sphingosine-kinase-1-independent-pathways
#18
Wisam H Al-Shujairi, Jennifer N Clarke, Lorena T Davies, Mohammed Alsharifi, Stuart M Pitson, Jillian M Carr
We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28095433/bj-3105-a-6-alkoxypyridin-3-ol-analog-impairs-t-cell-differentiation-and-prevents-experimental-autoimmune-encephalomyelitis-disease-progression
#19
Maheshwor Timilshina, Youra Kang, Ishmit Dahal, Zhiwei You, Tae-Gyu Nam, Keuk-Jun Kim, Byeong-Seon Jeong, Jae-Hoon Chang
CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement...
2017: PloS One
https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#20
Karl B Alstadhaug, Randi Fykse Halstensen, Francis Odeh
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML. CASE DESCRIPTION: A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis...
December 14, 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
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