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https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#1
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529928/the-probiotic-compound-vsl-3-modulates-mucosal-peripheral-and-systemic-immunity-following-murine-broad-spectrum-antibiotic-treatment
#2
Ira Ekmekciu, Eliane von Klitzing, Ulrike Fiebiger, Christian Neumann, Petra Bacher, Alexander Scheffold, Stefan Bereswill, Markus M Heimesaat
There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529001/a-single-intranasal-administration-of-virus-like-particle-vaccine-induces-an-efficient-protection-for-mice-against-human-respiratory-syncytial-virus
#3
Yue-Ying Jiao, Yuan-Hui Fu, Yi-Fei Yan, Ying Hua, Yao Ma, Xiu-Juan Zhang, Jing-Dong Song, Xiang-Lei Peng, Jiaqiang Huang, Tao Hong, Jin-Sheng He
Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully...
May 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#4
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#5
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521477/t-cell-immunity-induced-by-a-bivalent-salmonella-based-ceacam6-and-4-1bbl-vaccines-in-a-rat-colorectal-cancer-model
#6
Chunhui Jin, Xiaoqing Duan, Yingying Liu, Jianhong Zhu, Ke Zhang, Yuanting Zhang, Tingting Xia, Yajun Fei, Jianxin Ye
The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4-1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520183/infected-malnourished-children-displayed-changes-in-early-activation-and-lymphocyte-subpopulations
#7
Oralia Nájera-Medina, Fernando Valencia-Chavarría, Consuelo Cortés-Bejar, Monika Palacios-Martínez, C Paulina Rodríguez-López, María Cristina González-Torres
AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells were assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes...
May 18, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28512992/association-of-cd8-t-cells-with-bone-erosion-in-patients-with-rheumatoid-arthritis
#8
Young Bin Joo, Youngho Park, Kwangwoo Kim, So-Young Bang, Sang-Cheol Bae, Hye-Soon Lee
AIM: Bone erosion is a major problem worsening quality of rheumatoid arthritis (RA) patients' lives. However, causal factors responsible for bone erosion in RA have remained unclear. We aimed to examine genetic variants conferring bone erosion in RA using a Korean genome-wide association study (GWAS) and to search for possible biological mechanisms underlying the development of bone erosion. METHOD: We obtained genome-wide single nucleotide polymorphism (SNP) data for 711 Korean RA patients using Illumina HapMap 550v3/660W arrays...
May 16, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28503929/rare-control-of-sivmac239-infection-in-a-vaccinated-rhesus-macaque
#9
Mauricio de Aguiar Martins, Damien C Tully, Young C Shin, Lucas Gonzalez-Nieto, Kim Weisgrau, David J Bean, Rujuta Gadgil, Martin J Gutman, Aline Domingues, Helen Skye Maxwell, Diogo Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Michael Cruz, Noemia S Lima, Myrna Bonaldo, John Altman, Eva Rakasz, Saverio Capuano, Keith Reimann, Michael Piatak, Jeffrey Lifson, Ronald Desrosiers, Todd Allen, David Watkins
Effector memory T-cell (T<sub>EM</sub>) responses display potent antiviral properties and have been linked to stringent control of simian immunodeficiency virus (SIV) replication. Since recurrent antigen stimulation drives the differentiation of CD8<sup>+</sup> T-cells toward the T<sub>EM</sub> phenotype, here we incorporated a persistent herpesviral vector into a heterologous prime/boost/boost vaccine approach in order to maximize the induction of T<sub>EM</sub> responses...
May 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28502128/belatacept-resistant-rejection-is-associated-with-cd28-memory-cd8-t-cells
#10
D V Mathews, W C Wakwe, S C Kim, M C Lowe, C Breeden, M E Roberts, A B Farris, E A Strobert, J B Jenkins, C P Larsen, M L Ford, R Townsend, A B Adams
Recently newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent is associated with superior patient survival and graft function than traditional therapy but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely employed...
May 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28500232/nkg2d-ligand-targeted-bispecific-t-cell-engagers-lead-to-robust-antitumor-activity-against-diverse-human-tumors
#11
Claire Godbersen, Tiffany A Coupet, Amelia M Huehls, Tong Zhang, Michael B Battles, Jan L Fisher, Marc S Ernstoff, Charles L Sentman
Two new bispecific T cell engaging (BiTE) molecules with specificity for NKG2D ligands were developed and functionally characterized. One, huNKG2D-OKT3, was derived from the extracellular portion of the human NKG2D receptor fused to a CD3ε binding single-chain variable fragment (scFv), known as OKT3. NKG2D has multiple ligands, including MICA, which are expressed by a variety of malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE format that targets MICA on tumor cells and CD3ε on human T cells...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28498568/reconstitution-of-immune-cell-populations-in-multiple-sclerosis-patients-after-autologous-stem-cell-transplantation
#12
REVIEW
Fredrick G Karnell, Dongxia Lin, Samantha Motley, Thomas Duhen, Noha Lim, Daniel J Campbell, Laurence A Turka, Holden T Maecker, Kristina M Harris
Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. In a phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) hematopoietic stem cell transplant resulted in 69.2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new MRI lesions through year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post HSCT and the impact of treatment on the phenotype of circulating T cells in this study population...
May 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28490594/dok-1-and-dok-2-are-required-to-maintain-herpes-simplex-virus-1-specific-cd8-t-cells-in-a-murine-model-of-ocular-infection
#13
Soumia Lahmidi, Mitra Yousefi, Slimane Dridi, Pascale Duplay, Angela Pearson
Dok-1 and Dok-2 negatively regulate responses downstream of several immune receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins are essential in the formation of memory CD8(+) T cells to an exogenous epitope expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the control of viral infection is unknown. Herein, we investigated the role of Dok proteins in modulating the immune response against herpes simplex virus 1 (HSV-1) in a mouse model of ocular infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28490440/human-memory-cd8-t-cell-effector-potential-is-epigenetically-preserved-during-in-vivo-homeostasis
#14
Hossam A Abdelsamed, Ardiana Moustaki, Yiping Fan, Pranay Dogra, Hazem E Ghoneim, Caitlin C Zebley, Brandon M Triplett, Rafick-Pierre Sekaly, Ben Youngblood
Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression...
May 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28488272/pathophysiological-characteristics-of-preproinsulin-specific-cd8-t-cells-in-subjects-with-juvenile-onset-and-adult-onset-type-1-diabetes-a-1-year-follow-up-study
#15
Mahinder Paul, Darshan Badal, Neenu Jacob, Devi Dayal, Rakesh Kumar, Anil Bhansali, Sanjay Kumar Bhadada, Naresh Sachdeva
AIMS/HYPOTHESIS: Among the beta-cell associated antigens, preproinsulin (PPI) has been shown to play a key role in the pathogenesis of type 1 diabetes (T1D). PPI-specific autoreactive CD8+ T cells emerge early during beta-cell destruction and persist in peripheral circulation during diabetes progression. However, the influence of insulin therapy on phenotype of autoreactive CD8+ T cells in T1D including, juvenile-onset T1D (JOT1D), and adult-onset T1D (AOT1D) is not yet known. METHODS: We followed the time course of PPI-specific CD8+ T cells in JOT1D and AOT1D subjects that achieved glycemic control after 1 year of insulin therapy, using major histocompatibility complex-I (MHC-I) dextramers by flow cytometry...
May 10, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#16
Elizabeth Whittaker, Mark Nicol, Heather J Zar, Beate Kampmann
BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection. OBJECTIVE: To comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487567/a-robust-in-vitro-model-for-trans-lymphatic-endothelial-migration
#17
Yanbao Xiong, C Colin Brinkman, Konrad S Famulski, Emmanuel F Mongodin, Colin J Lord, Keli L Hippen, Bruce R Blazar, Jonathan S Bromberg
Trans-endothelial migration (TEM) is essential for leukocyte circulation. While much is known about trans-blood endothelial migration, far less is known about trans-lymphatic endothelial migration. We established an in vitro system to evaluate lymphatic TEM for various cell types across primary mouse and human lymphatic endothelial cells (LEC), and validated the model for the murine LEC cell line SVEC4-10. T cells exhibited enhanced unidirectional migration from the basal (abluminal) to the apical (luminal) surface across LEC, whereas for blood endothelial cells (BEC) they migrated similarly in both directions...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28485322/role-of-triggering-receptor-expressed-on-myeloid-cell-1-expression-in-mammalian-target-of-rapamycin-modulation-of-cd8-t-cell-differentiation-during-the-immune-response-to-invasive-pulmonary-aspergillosis
#18
Na Cui, Hao Wang, Long-Xiang Su, Jia-Hui Zhang, Yun Long, Da-Wei Liu
BACKGROUND: Triggering receptor expressed on myeloid cell-1 (TREM-1) may play a vital role in mammalian target of rapamycin (mTOR) modulation of CD8+ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis (IPA). This study aimed to investigate whether the mTOR signaling pathway modulates the proliferation and differentiation of CD8+ T-cells during the immune response to IPA and the role TREM-1 plays in this process...
May 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28484450/il-2-mediated-in-vivo-expansion-of-regulatory-t-cells-combined-with-cd154-cd40-co-stimulation-blockade-but-not-ctla-4-ig-prolongs-allograft-survival-in-naive-and-sensitized-mice
#19
Lerisa Govender, Jean-Christophe Wyss, Rajesh Kumar, Manuel Pascual, Dela Golshayan
In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28482391/-two-families-of-x-linked-lymphoproliferative-disease-type-1-characterized-by-agammaglobulinemia
#20
W Y Li, J S Chen, Q Zhao, R X Dai, Y P Wang, H Y Zhao, X M Chen, X H Xue, X Y Sun, X M Tang, Y Zhang, Y Ding, X D Zhao, Z Y Zhang
Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry...
May 4, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
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