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Memory Stem T-Cells

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/29051183/development-of-t-cell-immunotherapy-for-hematopoietic-stem-cell-transplantation-recipients-at-risk-of-leukemia-relapse
#9
Robson G Dossa, Tanya Cunningham, Daniel Sommermeyer, Indira Medina-Rodriguez, Melinda A Biernacki, Kimberly Foster, Marie Bleakley
Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective anti-leukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T cell receptors (TCR) isolated from minor H antigen-specific T cells represent an untapped resource for developing targeted T cell immunotherapy to manage post-HCT leukemic relapse...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29045388/inflammatory-memory-sensitizes-skin-epithelial-stem-cells-to-tissue-damage
#10
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 26, 2017: Nature
https://www.readbyqxmd.com/read/29035156/cd4-t-memory-stem-cells-correlate-with-disease-progression-in-chronically-hiv-1-infected-patients
#11
Xiaofan Lu, Bingbing Song, Wenjia Weng, Huan Xia, Bin Su, Hao Wu, Tong Zhang, Wei Li, Yanqing Gao
Recently identified T memory stem (Tscm) cells have stem-cell-like properties, including long lifespan, self-renewal capacity, and multipotency to differentiate into other memory T cell types. In the study of simian immunodeficiency virus (SIV) infection, selective depletion of CCR5(+)CD4(+) Tscm cells and the high proliferation rate of these cells are believed to be responsible for the pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study to investigate the influence of chronic human immunodeficiency virus (HIV)-1 infection on CD4(+) Tscm cell homeostasis, and the effect of antiretroviral therapy (ART) on CD4(+) Tscm cells...
November 2017: Viral Immunology
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#12
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28994018/memory-cd4-t-cell-subsets-in-tumor-draining-lymph-nodes-of-breast-cancer-patients-a-focus-on-t-stem-cell-memory-cells
#13
Yasmin Vahidi, Zahra Faghih, Abdol-Rasoul Talei, Mehrnoosh Doroudchi, Abbas Ghaderi
BACKGROUND: The compartments of memory T cells play a fundamental role in the immune system by substantiating specific and acquired immunity. A new subset of memory cells, T stem cell memory (TSCM) cells, with stem cell-like properties, a high capacity to proliferate, a long survival, and an ability to differentiate into all effector and memory cells has recently been introduced. In the present study, we aimed to determine the frequency of CD4(+) TSCM and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients...
October 9, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28979262/cd28-blockade-ex-vivo-induces-alloantigen-specific-immune-tolerance-but-preserves-t-cell-pathogen-reactivity
#14
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935847/cd56-bright-natural-killer-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-graft-versus-host-disease-the-canadian-blood-and-marrow-transplant-group-randomized-0601-study-results
#15
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Sylvie Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeem Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephan Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
November 2017: Haematologica
https://www.readbyqxmd.com/read/28934393/neurofibromatosis-type-1-alternative-splicing-is-a-key-regulator-of-ras-erk-signaling-and-learning-behaviors-in-mice
#16
Hieu T Nguyen, Melissa N Hinman, Xuan Guo, Alok Sharma, Hiroyuki Arakawa, Guangbin Luo, Hua Lou
Appropriate activation of the Ras/extracellular signal-regulated kinase (ERK) protein signaling cascade within the brain is crucial for optimal learning and memory. One key regulator of this cascade is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by converting active Ras is bound to guanosine triphosphate, activating Ras into inactive Ras is bound to guanosine diphosphate, inactivating Ras. A previous study using embryonic stem cells and embryonic stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alternative splicing of Nf1 exon 23a...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#17
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28904110/the-chromatin-accessibility-signature-of-human-immune-aging-stems-from-cd8-t-cells
#18
Duygu Ucar, Eladio J Márquez, Cheng-Han Chung, Radu Marches, Robert J Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L Stitzel, A Karolina Palucka, George A Kuchel, Jacques Banchereau
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28861081/14%C3%A2-years-after-discovery-clinical-follow-up-on-15-patients-with-inducible-co-stimulator-deficiency
#19
Johanna Schepp, Janet Chou, Andrea Skrabl-Baumgartner, Peter D Arkwright, Karin R Engelhardt, Sophie Hambleton, Tomohiro Morio, Ekkehard Röther, Klaus Warnatz, Raif Geha, Bodo Grimbacher
BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855514/hit-and-run-programming-of-therapeutic-cytoreagents-using-mrna-nanocarriers
#20
H F Moffett, M E Coon, S Radtke, S B Stephan, L McKnight, A Lambert, B L Stoddard, H P Kiem, M T Stephan
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells...
August 30, 2017: Nature Communications
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