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Memory Stem T-Cells

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https://www.readbyqxmd.com/read/28443098/the-lysine-methyltransferase-g9a-in-immune-cell-differentiation-and-function
#1
REVIEW
Sebastian Scheer, Colby Zaph
G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is associated with gene silencing and acts primarily through the recruitment of H3K9me2-binding proteins that prevent transcriptional activation. Gene repression via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for the development of cellular lineages by repressing expression of pluripotency factors. In the immune system, lymphoid cells such as T cells and innate lymphoid cells (ILCs) can differentiate from a naïve state into one of several effector lineages that require both activating and repressive mechanisms to maintain the correct gene expression program...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#2
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432326/a-novel-mechanism-linking-memory-stem-cells-with-innate-immunity-in-protection-against-hiv-1-infection
#3
Yufei Wang, Trevor Whittall, Stuart Neil, Gary Britton, Mukesh Mistry, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Xuesong Yu, Alicia Sato, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Jerome H Kim, Thomas Lehner
HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4(+) T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426690/phenotypic-characterization-and-anticancer-capacity-of-cd8-cytokine-induced-killer-cells-after-antigen-induced-expansion
#4
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#5
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28411126/low-interleukin-2-concentration-favors-generation-of-early-memory-t-cells-over-effector-phenotypes-during-chimeric-antigen-receptor-t-cell-expansion
#6
Tanja Kaartinen, Annu Luostarinen, Pilvi Maliniemi, Joni Keto, Mikko Arvas, Heini Belt, Jonna Koponen, Angelica Loskog, Satu Mustjoki, Kimmo Porkka, Seppo Ylä-Herttuala, Matti Korhonen
BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype...
April 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#7
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28399164/sequential-monitoring-of-lymphocyte-subsets-and-of-t-and-b-cell-neogenesis-indexes-to-identify-time-varying-immunologic-profiles-in-relation-to-graft-versus-host-disease-and-relapse-after-allogeneic-stem-cell-transplantation
#8
Cristina Skert, Simone Perucca, Marco Chiarini, Viviana Giustini, Alessandra Sottini, Claudia Ghidini, Stefano Martellos, Federica Cattina, Benedetta Rambaldi, Valeria Cancelli, Michele Malagola, Alessandro Turra, Nicola Polverelli, Simona Bernardi, Luisa Imberti, Domenico Russo
T and B lymphocyte subsets have been not univocally associated to Graft-versus-host disease (GVHD) and relapse of hematological malignancies after stem cell transplantation (SCT). Their sequential assessment together with B and T cell neogenesis indexes has been not thoroughly analysed in relation to these changing and interrelated immunologic/clinic events yet. Lymphocyte subsets in peripheral blood (PB) and B and T cell neogenesis indexes were analysed together at different time points in a prospective study of 50 patients...
2017: PloS One
https://www.readbyqxmd.com/read/28368375/multiple-myeloma-patients-in-long-term-complete-response-after-autologous-stem-cell-transplantation-express-a-particular-immune-signature-with-potential-prognostic-implication
#9
A Arteche-López, A Kreutzman, A Alegre, P Sanz Martín, B Aguado, M González-Pardo, M Espiño, L M Villar, D García Belmonte, R de la Cámara, C Muñoz-Calleja
The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC)...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28361085/human-stem-memory-t-cells-tscm-as-critical-players-in-the-long-term-persistence-of-immune-responses
#10
Alexandre Morrot
No abstract text is available yet for this article.
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28351997/mitochondrial-protein-fus1-tusc2-in-premature-aging-and-age-related-pathologies-critical-roles-of-calcium-and-energy-homeostasis
#11
Roman Uzhachenko, Kelli Boyd, Danyvid Olivares-Villagomez, Yueming Zhu, J Shawn Goodwin, Tanu Rana, Anil Shanker, Winston J T Tan, Tanya Bondar, Ruslan Medzhitov, Alla V Ivanova
Decreased energy production and increased oxidative stress are considered to be major contributors to aging and aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss of a small mitochondrial protein Fus1 that maintains mitochondrial homeostasis results in premature aging, aging-associated pathologies, and decreased survival. We showed that Fus1KO mice develop multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death...
March 26, 2017: Aging
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#12
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/28329703/successful-and-maladaptive-t-cell-aging
#13
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28293817/cd4-memory-t-cells-retain-surface-expression-of-cd31-independently-of-thymic-function-in-patients-with-lymphoproliferative-disorders-following-autologous-hematopoietic-stem-cell-transplantation
#14
Egor V Batorov, Marina A Tikhonova, Irina V Kryuchkova, Vera V Sergeevicheva, Svetlana A Sizikova, Galina Y Ushakova, Dariya S Batorova, Andrey V Gilevich, Alexander A Ostanin, Ekaterina Y Shevela, Elena R Chernykh
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4(+)CD45RA(+)CD31(+) T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4(+)CD45RA(-)CD31(+) T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT...
March 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28284008/effective-and-persistent-antitumor-activity-of-her2-directed-car-t-cells-against-gastric-cancer-cells-in-vitro-and-xenotransplanted-tumors-in-vivo
#15
Yanjing Song, Chuan Tong, Yao Wang, Yunhe Gao, Hanren Dai, Yelei Guo, Xudong Zhao, Yi Wang, Zizheng Wang, Weidong Han, Lin Chen
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties...
March 10, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28281429/single-centre-experience-of-allogeneic-haemopoietic-stem-cell-transplant-in-paediatric-patients-in-cape-town-south-africa
#16
A Van Eyssen, N Novitsky, P De Wit, T Schlaphoff, V Thomas, D Pillay, M Hendricks, A Davidson
BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS)...
February 27, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28280003/epigenetic-memory-in-response-to-environmental-stressors
#17
Paolo Vineis, Aristotelis Chatziioannou, Vincent T Cunliffe, James M Flanagan, Mark Hanson, Micheline Kirsch-Volders, Soterios Kyrtopoulos
Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28279965/lower-levels-of-vitamin-a-are-associated-with-increased-gastrointestinal-graft-versus-host-disease-in-children
#18
Dana T Lounder, Pooja Khandelwal, Christopher Dandoy, Sonata Jodele, Michael Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley Teusink-Cross, Kelly Lake, Stella M Davies
Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce risk of graft versus host disease through reduced intestinal permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 post-transplant...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28275376/immunological-balance-is-associated-with-clinical-outcome-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes
#19
Kelen C R Malmegrim, Júlia T C de Azevedo, Lucas C M Arruda, Joana R F Abreu, Carlos E B Couri, Gislane L V de Oliveira, Patricia V B Palma, Gabriela T Scortegagna, Ana B P L Stracieri, Daniela A Moraes, Juliana B E Dias, Fabiano Pieroni, Renato Cunha, Luiza Guilherme, Nathália M Santos, Milton C Foss, Dimas T Covas, Richard K Burt, Belinda P Simões, Júlio C Voltarelli, Bart O Roep, Maria C Oliveira
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8(+) T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28261198/a-fas-hi-lymphoproliferative-phenotype-reveals-non-apoptotic-fas-signaling-in-htlv-1-associated-neuroinflammation
#20
Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, Saul V Schnitman, Ramon Kruschewsky, Giovanni López, Carolina Alvarez, Michael Talledo, Eduardo Gotuzzo, Douglas F Nixon, Jurgen Vercauteren, David Brassat, Roland Liblau, Anne Mieke Vandamme, Bernardo Galvão-Castro, Johan Van Weyenbergh
Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas(hi) T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP...
2017: Frontiers in Immunology
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