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Memory Stem T-Cells

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28228650/haematopoietic-stem-cell-transplantation-for-autoimmune-diseases
#8
REVIEW
Joost F Swart, Eveline M Delemarre, Femke van Wijk, Jaap-Jan Boelens, Jürgen Kuball, Jacob M van Laar, Nico M Wulffraat
Autologous haematopoietic stem cell transplantation (HSCT) is the only treatment that is able to induce long-term, drug-free and symptom-free remission in several refractory autoimmune rheumatic diseases. Over 3,000 HSCT procedures for rheumatic and nonrheumatic severe autoimmune diseases have been performed worldwide. Specific conditioning regimens are currently used to eradicate the autoreactive immunological memory of patients. Although in vivo immune cell depletion with antithymocyte globulin or anti-CD52 is the norm for many regimens, ex vivo selection of CD34(+) stem cells from the graft is controversial...
April 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#9
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
March 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28139337/graft-versus-leukemia-effect-with-a-wt1-specific-t-cell-response-induced-by-azacitidine-and-donor-lymphocyte-infusions-after-allogeneic-hematopoietic-stem-cell-transplantation
#10
Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashima, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto
BACKGROUND: Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation...
January 27, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28138559/transient-stimulation-expands-superior-antitumor-t-cells-for-adoptive-therapy
#11
Yuki Kagoya, Munehide Nakatsugawa, Toshiki Ochi, Yuchen Cen, Tingxi Guo, Mark Anczurowski, Kayoko Saso, Marcus O Butler, Naoto Hirano
Adoptive cell therapy is a potentially curative therapeutic approach for patients with cancer. In this treatment modality, antitumor T cells are exponentially expanded in vitro prior to infusion. Importantly, the results of recent clinical trials suggest that the quality of expanded T cells critically affects their therapeutic efficacy. Although anti-CD3 mAb-based stimulation is widely used to expand T cells in vitro, a protocol to generate T cell grafts for optimal adoptive therapy has yet to be established...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28138558/circulating-cxcr5-cxcr3-pd-1-lo-tfh-like-cells-in-hiv-1-controllers-with-neutralizing-antibody-breadth
#12
Enrique Martin-Gayo, Jacqueline Cronin, Taylor Hickman, Zhengyu Ouyang, Madelene Lindqvist, Kellie E Kolb, Julian Schulze Zur Wiesch, Rafael Cubas, Filippos Porichis, Alex K Shalek, Jan van Lunzen, Elias K Haddad, Bruce D Walker, Daniel E Kaufmann, Mathias Lichterfeld, Xu G Yu
HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5(+)CXCR3(+)PD-1(lo) CD4(+) T cells...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28060797/t-memory-stem-cells-in-health-and-disease
#13
REVIEW
Luca Gattinoni, Daniel E Speiser, Mathias Lichterfeld, Chiara Bonini
T memory stem (TSCM) cells are a rare subset of memory lymphocytes endowed with the stem cell-like ability to self-renew and the multipotent capacity to reconstitute the entire spectrum of memory and effector T cell subsets. Cumulative evidence in mice, nonhuman primates and humans indicates that TSCM cells are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM cells, owing to their extreme longevity and robust potential for immune reconstitution, are central players in many physiological and pathological human processes...
January 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28057064/the-lncrnas-involved-in-mouse-airway-allergic-inflammation-following-induced-pluripotent-stem-cell-mesenchymal-stem-cell-treatment
#14
Shu-Yue Wang, Xing-Liang Fan, Qiu-Ning Yu, Meng-Xia Deng, Yue-Qi Sun, Wen-Xiang Gao, Cheng-Lin Li, Jian-Bo Shi, Qing-Ling Fu
BACKGROUND: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear. METHODS: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28034872/fetal-and-adult-progenitors-give-rise-to-unique-populations-of-cd8-t-cells
#15
Jocelyn Wang, Erin M Wissink, Neva B Watson, Norah L Smith, Andrew Grimson, Brian D Rudd
During the ontogeny of the mammalian immune system, distinct lineages of cells arise from fetal and adult hematopoietic stem cells (HSCs) during specific stages of development. However, in some cases, the same immune cell type is produced by both HSC populations, resulting in the generation of phenotypically similar cells with distinct origins and divergent functional properties. In this report, we demonstrate that neonatal CD8(+) T cells preferentially become short-lived effectors and adult CD8(+) T cells selectively form long-lived memory cells after infection because they are derived from distinct progenitor cells...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28027219/cancer-risk-after-fat-transfer-a-multicenter-case-cohort-study
#16
Terence M Myckatyn, I Janelle Wagner, Babak J Mehrara, Melissa A Crosby, Julie E Park, Bahjat F Qaqish, Dominic T Moore, Evan L Busch, Amanda K Silva, Surinder Kaur, David W Ollila, Clara N Lee
BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers...
January 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28018990/the-tcf1-bcl6-axis-counteracts-type-i-interferon-to-repress-exhaustion-and-maintain-t-cell-stemness
#17
Tuoqi Wu, Yun Ji, E Ashley Moseman, Haifeng C Xu, Monica Manglani, Martha Kirby, Stacie M Anderson, Robin Handon, Elizabeth Kenyon, Abdel Elkahloun, Weiwei Wu, Philipp A Lang, Luca Gattinoni, Dorian B McGavern, Pamela L Schwartzberg
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1(high) and a more exhausted TCF1(low) population. Virus-specific TCF1(high) CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1(low) cells and act as progenitor cells to replenish TCF1(low) cells...
December 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/27998208/increasing-stem-cell-dose-promotes-posttransplant-immune-reconstitution
#18
Ning Xu, Sylvie Shen, Alla Dolnikov
Umbilical cord blood (UCB) transplantation can provide a successful therapeutic option for patients that have no suitable related donor. UCB transplantation is often limited by the relatively small hematopoietic stem cell (HSC) numbers in UCB especially for adult recipients. Early neutrophil and platelet engraftment correlates with the stem cell numbers in UCB transplant. Compared to other HSC sources, immune reconstitution following UCB transplant is slower and complicated by increased frequency of opportunistic infections...
January 16, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27997758/comprehensive-mass-cytometry-analysis-of-cell-cycle-activation-and-co-inhibitory-receptors-expression-in-cd4-t-cells-from-healthy-and-hiv-infected-individuals
#19
REVIEW
Aurélien Corneau, Antonio Cosma, Sophie Even, Christine Katlama, Roger Legrand, Véronique Frachet, Catherine Blanc, Brigitte Autran
RATIONALE: Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells. METHODS: peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors (HD) and 4 HIV-infected on anti-retroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intra-cellular markers of differentiation, activation, exhaustion and cell cycle stages...
December 20, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27974195/human-stem-cell-like-memory-t-cells-are-maintained-in-a-state-of-dynamic-flux
#20
Raya Ahmed, Laureline Roger, Pedro Costa Del Amo, Kelly L Miners, Rhiannon E Jones, Lies Boelen, Tinhinane Fali, Marjet Elemans, Yan Zhang, Victor Appay, Duncan M Baird, Becca Asquith, David A Price, Derek C Macallan, Kristin Ladell
Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water...
December 13, 2016: Cell Reports
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