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https://www.readbyqxmd.com/read/28625015/crispr-cas9-mediated-lag-3-disruption-in-car-t-cells
#1
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang
T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture...
June 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28511640/tryptophan-catabolism-and-immune-activation-in-primary-and-chronic-hiv-infection
#2
Marco Gelpi, Hans J Hartling, Per M Ueland, Henrik Ullum, Marius Trøseid, Susanne D Nielsen
BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation. METHODS: Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19))...
May 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28495618/a-model-of-acute-renal-allograft-rejection-in-outbred-yorkshire-piglets
#3
Randi Lassiter, Youli Wang, Xuexiu Fang, Matt Winn, Arina Ghaffari, Chak-Sum Ho, Sandra Helman, Ryan Jajosky, Daniel Kleven, N Stanley Nahman, Todd D Merchen
Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation...
May 8, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28468883/cxcl10-cxcr3-dependent-mobilization-of-hsv-specific-cd8-tem-and-cd8-trm-cells-within-infected-tissues-allows-efficient-protection-against-recurrent-herpes-infection-and-disease
#4
Ruchi Srivastava, Arif A Khan, Sravya Chilukuri, Sabrina A Syed, Tien T Tran, Julie Furness, Elmostafa Bahraoui, Lbachir BenMohamed
Herpes simplex virus type 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8(+) T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXCL10/CXCR3 chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8(+) T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8(+) T cell responses to recurrent ocular herpes infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28388647/impact-of-probiotic-saccharomyces-boulardii-on-the-gut-microbiome-composition-in-hiv-treated-patients-a-double-blind-randomised-placebo-controlled-trial
#5
Judit Villar-García, Robert Güerri-Fernández, Andrés Moya, Alicia González, Juan J Hernández, Elisabet Lerma, Ana Guelar, Luisa Sorli, Juan P Horcajada, Alejandro Artacho, Giuseppe D Auria, Hernando Knobel
Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load)...
2017: PloS One
https://www.readbyqxmd.com/read/28284725/altered-helper-t-cell-mediated-immune-responses-in-male-mice-conceived-through-in-vitro-fertilization
#6
Hiwa Karimi, Pooya Mahdavi, Shohreh Fakhari, Mohammad Reza Faryabi, Parisa Esmaeili, Omid Banafshi, Ebrahim Mohammadi, Fardin Fathi, Aram Mokarizadeh
A study using a mouse IVF model was conducted to examine the hypothesis that in vitro fertilization (IVF) treatment may lead to immune system alteration in the offspring. Phagocytic activity and lymphocyte proliferative responses to mitogen, alloantigen, and purified protein derivative (PPD) of Mycobacterium bovis were investigated in the splenocytes of BCG-treated male mice conceived by IVF or natural conception. Intracellular expression of T-bet and GATA3 in helper T-cell population were examined in both groups...
March 9, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28242002/canine-peripheral-blood-cd4-cd8-double-positive-tcell-subpopulations-exhibit-distinct-tcell-phenotypes-and-effector-functions
#7
Kathrin Rothe, Doris Bismarck, Mathias Büttner, Gottfried Alber, Heiner von Buttlar
Canine peripheral blood CD4(+)CD8α(+) double-positive (dp) Tcells represent a small population of T lymphocytes that are not only derived from single-positive (sp) CD4(+) but also from CD8(+) Tcells. Dp Tcells can be subdivided in three different subpopulations according to their expression levels of CD4 and CD8α, i.e. the CD4(dim)CD8α(bright), CD4(bright)CD8α(bright), and the CD4(bright)CD8α(dim) subsets. Previously we could show that total canine peripheral CD4(+)CD8α(+) dp Tcells have features of activated Tcells...
March 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28220979/more-significance-of-tb-igra-except-for-the-diagnose-of-tuberculosis
#8
Jun-Chi Xu, Ze-Yi Li, Xin-Nian Chen, Cui-Lin Shi, Mei-Ying Wu, Hui Chen, Xiao-Yan Zhu, Hua-Feng Song, Min-Juan Wu, Ping Xu
OBJECTIVE: Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. DESIGN: A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015...
February 21, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28192476/th40-cells-cd4-cd40-tcells-drive-a-more-severe-form-of-experimental-autoimmune-encephalomyelitis-than-conventional-cd4-t-cells
#9
Gisela M Vaitaitis, Martin G Yussman, Dan M Waid, David H Wagner
CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination...
2017: PloS One
https://www.readbyqxmd.com/read/28133077/-a-case-of-angioimmunoblastic-t-cell-lymphoma-merged-with-colorectal-cancer-that-we-were-able-to-resect-after-a-chemotherapy-response
#10
Masaya Higashiguchi, Kenji Sakai, Teruyuki Kobayashi, Takashi Doi, Taichi Koyama, Minako Hoshi, Hirokazu Taniguchi, Masakazu Murakami, Kimimasa Ikeda, Eiji Kurokawa, Itsuko Nakamichi
The patient was 77-year-old man. He visited our hospital with the chief complaint of an abdominal mass in March 2015. We diagnosed the patient with transverse colon cancer and he was suspected of having malignant lymphoma. In March 2016, we attempted to perform right hemicolectomy for the transverse colon cancer, but it was difficult because swollen lymph nodes had formed a large mass with the surrounding tissue, including vessels of the mesentery. We could only complete the surgery after mesenteric lymph node biopsy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27930978/mechanism-of-action-and-effect-of-immune-modulating-agents-in-the-treatment-of-psoriasis
#11
Rehab M El-Gharabawy, Amira S Ahmed, Amal H Al-Najjar
OBJECTIVES: The aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis. SUBJECTS AND METHODS: One hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27847359/human-asymptomatic-epitopes-identified-from-the-herpes-simplex-virus-tegument-protein-vp13-14-ul47-preferentially-recall-polyfunctional-effector-memory-cd44high-cd62llow-cd8-tem-cells-and-protect-humanized-hla-a-02-01-transgenic-mice-against-ocular-herpesvirus
#12
Ruchi Srivastava, Arif A Khan, Sumit Garg, Sabrina A Syed, Julie N Furness, Hawa Vahed, Tiffany Pham, Howard T Yu, Anthony B Nesburn, Lbachir BenMohamed
Herpes simplex virus 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8(+) T cells play a role in the natural protection seen in asymptomatic (ASYMP) individuals (individuals who have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8(+) T-cell epitopes from the 693-amino-acid sequence of the VP13/14 protein...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27625431/cytokines-and-t-cell-homeostasis-in-hiv-infection
#13
REVIEW
Michael L Freeman, Carey L Shive, Thao P Nguyen, Souheil-Antoine Younes, Soumya Panigrahi, Michael M Lederman
Untreated human immunodeficiency virus (HIV) infection is characterized by progressive CD4(+) T-cell depletion and CD8(+) T-cell expansion, and CD4(+) T-cell depletion is linked directly to the risk for opportunistic infections and infection-associated mortality. With suppression of HIV replication by antiretroviral therapy, circulating CD4(+) Tcell numbers typically improve while CD8(+) T-cell expansion persists, and both CD4(+) T-cell cytopenia and CD8(+) T-cell expansion are associated with morbidity and mortality...
October 1, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27522716/-subpopulations-of-regulatory-t-lymphocytes-in-the-peripheral-blood-of-patients-with-rheumatoid-arthritis
#14
P N Kravchenko, G A Zhulai, A V Churov, E K Oleinik, V M Oleinik, O Yu Barysheva, N N Vezikova, I M Marusenko
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA...
2016: Vestnik Rossiĭskoĭ Akademii Meditsinskikh Nauk
https://www.readbyqxmd.com/read/27509944/incidence-and-management-of-toxicity-associated-with-lasparaginase-in-the-treatment-of-all-and-nk-tcell-lymphoma-an-observational-study
#15
MULTICENTER STUDY
Shu Hui Yeang, Alexandre Chan, Chuen Wen Tan, Soon Thye Lim, Heng Joo Ng
BACKGROUND: Lasparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/Tcell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations. MATERIALS AND METHODS: In this retrospective, multicenter, observational study, Asian patients ≥ 18 years old who received ≥ 1 dose of the native E...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27231509/t-cell-subset-profile-in-healthy-zambian-adults-at-the-university-teaching-hospital
#16
Caroline Cleopatra Chisenga, Paul Kelly
INTRODUCTION: Symptom-free human immunodeficiency virus antibody-negative Zambian adults (51 subjects, aged 20 to 62 years, 33.3% women and 66.7% men) were studied to establish T cell subset reference ranges. METHODS: We carried out across sectional study at the University Teaching Hospital, Lusaka. Blood samples were collected from healthy donor volunteers from hospital health care staff, between February and March 2015. Immunopheno typing was undertaken to characterize Tcell subsets using the markers CD3, CD4, CD8, α4β7, Ki67, CD25, CCR7, CD54RA, CD57, CD28, CD27 and HLA-DR...
2016: Pan African Medical Journal
https://www.readbyqxmd.com/read/27220625/gender-and-duration-of-disease-differentiate-responses-to-rituximab-dexamethasone-therapy-in-adults-with-immune-thrombocytopenia
#17
John Chapin, Christina S Lee, Haiyu Zhang, James L Zehnder, James B Bussel
Adults often develop chronic immune thrombocytopenia (ITP) for which treatment order is uncertain. Rituximab and three cycles of dexamethasone (4R + 3Dex) improve treatment responses and short-term disease control but long-term outcome is not known. In adults with ITP treated with 4R + 3D, we sought long-term outcome and associated prognostic variables. Forty-nine adults treated at Weill-Cornell received 4R + 3Dex. Their clinical characteristics were reviewed. Duration was median time to treatment failure; Kaplan-Meier estimates were developed...
September 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27217298/impact-of-human-mutant-tgf%C3%AE-1-fc-protein-on-memory-and-regulatory-t-cell-homeostasis-following-lymphodepletion-in-nonhuman-primates
#18
H Guo, L Lu, R Wang, A Perez-Gutierrez, H S Abdulkerim, A F Zahorchak, T L Sumpter, K A Reimann, A W Thomson, M B Ezzelarab
Transforming growth factor β1 (TGFβ1) plays a key role in T cell homeostasis and peripheral tolerance. We evaluated the influence of a novel human mutant TGFβ1/Fc (human IgG4 Fc) fusion protein on memory CD4(+) and CD8(+) T cell (Tmem) responses in vitro and their recovery following antithymocyte globulin (ATG)-mediated lymphodepletion in monkeys. TGFβ1/Fc induced Smad2/3 protein phosphorylation in rhesus and human peripheral blood mononuclear cells and augmented the suppressive effect of rapamycin on rhesus Tmem proliferation after either alloactivation or anti-CD3/CD28 stimulation...
October 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27141390/improved-efficacy-of-mitoxantrone-in-patients-with-castration-resistant-prostate-cancer-after-vaccination-with-gm-csf-transduced-allogeneic-prostate-cancer-cells
#19
Joyce M van Dodewaard-de Jong, Saskia Jam Santegoets, Peter M van de Ven, Jurjen Versluis, Henk M W Verheul, Tanja D de Gruijl, Winald R Gerritsen, Alfons J M van den Eertwegh
Previous vaccination studies in patients with castration-resistant prostate cancer (CRPC) showed improved survival without prolongation of progression-free survival (PFS). This might be explained by enhanced efficacy of subsequent therapies because of heightened immune status. We therefore evaluated the efficacy of chemotherapy in CRPC patients after immunotherapy. We retrospectively analyzed 28 patients who were treated with ipilimumab and GVAX, an allogeneic vaccine, and 21 patients who were randomized to GVAX or no vaccination...
April 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27070448/targeting-pd-1-and-tim-3-pathways-to-reverse-cd8-t-cell-exhaustion-and-enhance-ex-vivo-t-cell-responses-to-autologous-dendritic-tumor-vaccines
#20
Jingwei Liu, Shurong Zhang, Yuefeng Hu, Zhaomin Yang, Jingpo Li, Xuesong Liu, Lijuan Deng, Yue Wang, Xiaoyan Zhang, Ting Jiang, Xu Lu
The paradoxical coexistence of spontaneous tumor antigen-specific immune response with progressive disease in cancer patients need to dissect the molecular pathways involved in tumor-induced T-cell dysfunction or exhaustion. Programmed cell death 1 (PD-1) has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1-PD-L1 interactions has been shown to partially restore T-cell function. We have found that T-cell immunoglobulin mucin (Tim) 3 is expressed on CD8+ tumor-infiltrating lymphocytes (TILs) isolated from patients with colorectal cancer...
May 2016: Journal of Immunotherapy
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