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Memory Stem T-Cells

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https://www.readbyqxmd.com/read/29409351/cd33-specific-chimeric-antigen-receptor-t-cells-with-different-costimulators-showed-potent-anti-leukemia-efficacy-and-different-phenotype
#1
Saisai Li, Zhongfei Tao, Yingxi Xu, Jia Liu, Na An, Ying Wang, Haiyan Xing, Zheng Tian, Kejing Tang, Xiaolong Liao, Qing Rao, Min Wang, Jianxiang Wang
Acute myeloid leukemia (AML) is a kind of a malignant hematologic tumor caused by uncontrolled repopulation of myeloid hematopoietic stem cells (HSCs). Current therapeutic effects for AML patients are unsatisfactory. Especially relapsed and refractory AML still have poor prognosis. T cell modified by chimeric antigen receptor (CAR) is an immunotherapeutic strategy for malignancies, which has a broad developing prospect. Most of AML cells overexpress the myeloid antigen CD33. Therefore, CD33-specific CAR-T cells with different costimulators (CD28, 4-1BB or both, referred to as CD33 28z...
February 6, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29408330/new-human-combined-immunodeficiency-due-to-irf4-deficiency-inherited-by-uniparental-isodisomy
#2
María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela Del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía Del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo Del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L Corbí, Hugh T Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena
BACKGROUND: Interferon regulatory factor 4 (IRF4) is a fundamental transcription factor in adaptive and innate immunity, due to its key role in the differentiation and functional specialization of lymphoid and myeloid lineage cells. In mouse models, IRF4 participates in bone marrow central tolerance, naïve B cell activation, germinal centre formation, plasma cell differentiation, immunoglobulin secretion, T helper subset differentiation, macrophage polarization, and dendritic cell differentiation, among other processes...
February 2, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29358280/cytokine-and-tcr-mediated-regulation-of-t-cell-expression-of-ly6c-and-sca-1
#3
Jonathan H DeLong, Aisling O'Hara Hall, Christoph Konradt, Gaia M Coppock, Jeongho Park, Gretchen Harms Pritchard, Christopher A Hunter
Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4+ T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8+ memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-γ are potent inducers of Ly6C and Sca-1 in naive mouse CD4+ and CD8+ T cells, whereas TGF-β limits their expression...
January 22, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29358179/strategies-to-activate-nk-cells-to-prevent-relapse-and-induce-remission-following-hematopoietic-stem-cell-transplantation
#4
Sarah Cooley, Peter Parham, Jeffrey S Miller
Natural Killer (NK) cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. After allogeneic transplantation, NK cells are the first reconstituting lymphocytes, but are dysfunctional. Manipulating this first wave of lymphocytes could be instrumental in reducing the 40% relapse rate following transplantation with reduced intensity conditioning. NK cells express numerous activating and inhibitory receptors. Some recognize classical or non-classical HLA class I ligands, others recognize class I-like ligands or unrelated ligands...
January 22, 2018: Blood
https://www.readbyqxmd.com/read/29335016/autophagy-is-required-for-human-umbilical-cord-mesenchymal-stem-cells-to-improve-spatial-working-memory-in-app-ps1-transgenic-mouse-model
#5
Wen Li, Kai Li, Jing Gao, Zhuo Yang
BACKGROUND: Recent studies have shown that autophagy plays a central role in mesenchymal stem cells (MSCs), and many studies have shown that human umbilical cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of mechanisms. However, no studies have looked at the effects of autophagy on neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we investigated whether inhibition of autophagy could weaken or block the function of huMSCs through in vitro and in vivo experiments...
January 15, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29328786/connections-between-metabolism-and-epigenetics-in-programming-cellular-differentiation
#6
Danielle A Chisolm, Amy S Weinmann
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29326266/the-epigenetic-control-of-stemness-in-cd8-t-cell-fate-commitment
#7
Luigia Pace, Christel Goudot, Elina Zueva, Paul Gueguen, Nina Burgdorf, Joshua J Waterfall, Jean-Pierre Quivy, Geneviève Almouzni, Sebastian Amigorena
After priming, naïve CD8 + T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8 + T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell-related memory genes...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29296748/immune-signatures-associated-with-improved-progression-free-and-overall-survival-for-myeloma-patients-treated-with-ahsct
#8
Christine M Ho, Philip L McCarthy, Paul K Wallace, Yali Zhang, Ahmad Fora, Patrick Mellors, Joseph D Tario, Benjamin L S McCarthy, George L Chen, Sarah A Holstein, Sophia R Balderman, Xuefang Cao, Bruno Paiva, Theresa Hahn
Multiple therapeutic options exist for multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (AHSCT). Measurement of minimal residual disease (MRD) and immune reconstitution is rapidly becoming an integral part of the care of MM patients. We investigated comprehensive immune profiling (IP) associated with progression-free survival (PFS) and overall survival (OS). From August 2007 to January 2014, 101 consecutive MM patients underwent peripheral blood IP and marrow MRD testing before and approximately 100 days after AHSCT...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284679/mesenchymal-stem-cells-and-cell-derived-extracellular-vesicles-protect-hippocampal-neurons-from-oxidative-stress-and-synapse-damage-induced-by-amyloid-%C3%AE-oligomers
#9
Mariana A de Godoy, Leonardo M Saraiva, Luiza R P Carvalho, Andreia Vasconcelos-Dos-Santos, Hellen J V Beiral, Alane Bernardo Ramos, Livian R de Paula Silva, Renata B Leal, Victor H S Monteiro, Carolina V Braga, Carlla A de Araujo-Silva, Leandro C Sinis, Victor Bodart Santos, Tais Hanae Kasai Brunswick, Carolina de Lima Alcantara, Ana Paula C A Lima, Narcisa L da Cunha E Silva, Antonio Galina, Adalberto Vieyra, Fernanda G De Felice, Rosalia Mendez-Otero, Sergio T Ferreira
Alzheimer disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-beta peptide (AβOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AβOs on hippocampal neurons...
December 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29284044/long-term-persistence-and-function-of-hematopoietic-stem-cell-derived-chimeric-antigen-receptor-t-cells-in-a-nonhuman-primate-model-of-hiv-aids
#10
Anjie Zhen, Christopher W Peterson, Mayra A Carrillo, Sowmya Somashekar Reddy, Cindy S Youn, Brianna B Lam, Nelson Y Chang, Heather A Martin, Jonathan W Rick, Jennifer Kim, Nick C Neel, Valerie K Rezek, Masakazu Kamata, Irvin S Y Chen, Jerome A Zack, Hans-Peter Kiem, Scott G Kitchen
Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29276513/multidimensional-analysis-integrating-human-t-cell-signatures-in-lymphatic-tissues-with-sex-of-humanized-mice-for-prediction-of-responses-after-dendritic-cell-immunization
#11
Valery Volk, Andreas I Reppas, Philippe A Robert, Loukia M Spineli, Bala Sai Sundarasetty, Sebastian J Theobald, Andreas Schneider, Laura Gerasch, Candida Deves Roth, Stephan Klöss, Ulrike Koehl, Constantin von Kaisenberg, Constanca Figueiredo, Haralampos Hatzikirou, Michael Meyer-Hermann, Renata Stripecke
Mice transplanted with human cord blood-derived hematopoietic stem cells (HSCs) became a powerful experimental tool for studying the heterogeneity of human immune reconstitution and immune responses in vivo. Yet, analyses of human T cell maturation in humanized models have been hampered by an overall low immune reactivity and lack of methods to define predictive markers of responsiveness. Long-lived human lentiviral induced dendritic cells expressing the cytomegalovirus pp65 protein (iDCpp65) promoted the development of pp65-specific human CD8+ T cell responses in NOD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29259265/mast-cells-increase-adult-neural-precursor-proliferation-and-differentiation-but-this-potential-is-not-realized-in-vivo-under-physiological-conditions
#12
J M Wasielewska, L Grönnert, N Rund, L Donix, R Rust, A M Sykes, A Hoppe, A Roers, G Kempermann, T L Walker
There is growing evidence that both peripheral and resident immune cells play an important part in regulating adult neural stem cell proliferation and neurogenesis, although the contribution of the various immune cell types is still unclear. Mast cells, a population of immune cells known for their role in the allergic response, have been implicated in the regulation of adult hippocampal neurogenesis. Mast cell-deficient c-kitW-sh/W-sh mice have previously been shown to exhibit significantly decreased adult hippocampal neurogenesis and associated learning and memory deficits...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29197680/increased-co-expression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allo-sct
#13
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematological malignancy due to allo-reactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet, tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of co-stimulatory molecules and can up-regulate co-inhibitory molecules that, upon ligation with their counter receptors on the tumor-reactive T cells, inhibit T cell functionality...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29186194/human-t-cell-leukemia-virus-type-1-infects-multiple-lineage-hematopoietic-cells-in-vivo
#14
Rie Furuta, Jun-Ichirou Yasunaga, Michi Miura, Kenji Sugata, Akatsuki Saito, Hirofumi Akari, Takaharu Ueno, Norihiro Takenouchi, Jun-Ichi Fujisawa, Ki-Ryang Koh, Yusuke Higuchi, Mohamed Mahgoub, Masakazu Shimizu, Fumihiko Matsuda, Anat Melamed, Charles R Bangham, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+ effector/memory T cells in vivo. However, it remains unknown whether HTLV-1 preferentially infects these T cells or this virus converts infected precursor cells to specialized T cells. Expression of viral genes in vivo is critical to study viral replication and proliferation of infected cells. Therefore, we first analyzed viral gene expression in non-human primates naturally infected with simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes closely resemble those of HTLV-1...
November 29, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29176645/t-cell-receptor-%C3%AE-chains-display-abnormal-shortening-and-repertoire-sharing-in-type-1-diabetes
#15
Iria Gomez-Tourino, Yogesh Kamra, Roman Baptista, Anna Lorenc, Mark Peakman
Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2 × 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4+ T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is also observed in unproductive TCRB sequences, which are not subjected to thymic culling, suggesting that the shorter CDR3s arise independently of positive/negative selection...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#16
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29137227/re-balance-of-memory-t-cell-subsets-in-peripheral-blood-from-patients-with-cml-after-tki-treatment
#17
Danlin Yao, Ling Xu, Jiaxiong Tan, Yikai Zhang, Shuai Lu, Mingde Li, Sichun Lu, Lijian Yang, Shaohua Chen, Jie Chen, Jing Lai, Yuhong Lu, Xiuli Wu, Xianfeng Zha, Yangqiu Li
T cell immune surveillance is considered an important host protection process for inhibiting carcinogenesis. The full capacity of T cell immune surveillance is dependent on T cell homeostasis, particularly for central memory T (TCM) cells and stem cell memory T (TSCM) cells. In this study, distribution of T cell subsets in peripheral blood from 12 patients with chronic myeloid leukemia (CML) and 12 cases with CML in complete remission (CR) was analyzed using a multicolor flow cytometer, and 16 samples from healthy individuals (HIs) served as control...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29123962/distinctive-features-of-tumor-infiltrating-%C3%AE-%C3%AE-t-lymphocytes-in-human-colorectal-cancer
#18
S Meraviglia, E Lo Presti, M Tosolini, C La Mendola, V Orlando, M Todaro, V Catalano, G Stassi, G Cicero, S Vieni, J J Fourniè, F Dieli
γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5-90%) and 4% γδ T cells on average, with the majority expressing Vδ1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29115976/gmp-production-of-purified-human-b-lymphocytes-for-the-adoptive-transfer-in-patients-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Hannes Tittlbach, Andrea Schneider, Julian Strobel, Robert Zimmermann, Stefanie Maas, Bernd Gebhardt, Georg Rauser, Michael Mach, Andreas Mackensen, Thomas H Winkler, Julia Winkler
BACKGROUND: We have recently shown that memory B cells from murine CMV immune donor animals adoptively transferred into immunodeficient mice were highly effective in protecting from a viral infection indicating a therapeutic potential of virus specific memory B cells. These preclinical data provided evidence that a cell-based strategy supporting the humoral immune response might be effective in a clinical setting of immunodeficiency after allogeneic hematopoietic stem cell transplantation...
November 7, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29101105/cytokine-mediated-regulation-of-cd8-t-cell-responses-during-acute-and-chronic-viral-infection
#20
Masao Hashimoto, Se Jin Im, Koichi Araki, Rafi Ahmed
The common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, regulate critical aspects of antiviral CD8 T-cell responses. During acute infections, IL-2 controls expansion and differentiation of antiviral CD8 T cells, whereas IL-7 and IL-15 are key cytokines to maintain memory CD8 T cells long term in an antigen-independent manner. On the other hand, during chronic infections, in which T-cell exhaustion is established, precise roles of these cytokines in regulation of antiviral CD8 T-cell responses are not well defined...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
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