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https://www.readbyqxmd.com/read/29422902/t-cells-engaging-the-conserved-mhc-class-ib-molecule-qa-1b-with-tap-independent-peptides-are-semi-invariant-lymphocytes
#1
Elien M Doorduijn, Marjolein Sluijter, Bianca J Querido, Ursula J E Seidel, Claudia C Oliveira, Sjoerd H van der Burg, Thorbald van Hall
The HLA-E homolog in the mouse (Qa-1b) is a conserved MHC class Ib molecule presenting monomorphic peptides to germline-encoded natural killer receptor CD94/NKG2A. Previously, we demonstrated the replacement of this canonical peptide by a diverse peptidome upon deficiency of the TAP peptide transporter. Analysis of this Qa-1b-restricted T cell repertoire against these non-mutated neoantigens revealed characteristics of conventional hypervariable CD8+ T cells, but also of invariant T cell receptor (TCR)αβ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29367461/cd122-blockade-restores-immunological-tolerance-in-autoimmune-type-1-diabetes-via-multiple-mechanisms
#2
Xiaomei Yuan, Yi Dong, Naoya Tsurushita, J Yun Tso, Wenxian Fu
Signaling through IL-2/IL-15Rβ (CD122) is essential for the differentiation and function of T cells and NK cells. A mAb against CD122 has been implicated to suppress autoimmune type 1 diabetes (T1D) development in animal models. However, the mechanisms remain poorly understood. We find that in vivo administration of an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29328469/human-cytomegalovirus-ul141-protein-interacts-with-celf5-and-affects-viral-dna-replication
#3
Fei Zou, Zhi-Tao Lu, Shuang Wang, Si Wu, Ying-Ying Wu, Zheng-Rong Sun
Human cytomegalovirus (HCMV) infection is the primary viral cause of congenital abnormalities and mental retardation in newborns. The HCMV UL141‑encoded glycoprotein has been previously revealed to inhibit the cell‑surface expression of cluster of differentiation (CD)155, CD122, tumor necrosis factor‑related apoptosis‑inducing ligand death (TRAIL)‑receptor 1 (R1) and TRAIL‑receptor 2 (R2), thus protecting virally‑infected cells by allowing them to escape natural killer cell‑mediated cytotoxicity...
January 10, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#4
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29307521/decreased-cd122-on-cd56dim-nk-associated-with-its-impairment-in-asymptomatic-chronic-hbv-carriers-with-high-levels-of-hbv-dna-hbsag-and-hbeag
#5
Wenzheng Han, Qin Ni, Kezhou Liu, Yunliang Yao, Dejian Zhao, Xia Liu, Yu Chen
AIMS: NK cells play important roles in inhibiting HBV replication and preventing HBV infection. However, NK-cell dysfunction has not been fully studied in asymptomatic chronic HBV carriers (ASC). This study aims to assess decreased expression of CD122 associated with impaired NK cells and the restoration of NK cells with IL-2 and IL-15 stimulation. MAIN METHODS: The experiments were performed by flow cytometer, cytotoxicity assay, ELISA and Western blotting. KEY FINDINGS: The reduced CD122 on CD56+ NK cells and CD56dim NK cells is associated with high levels of HBV DNA, HBsAg or HBeAg in ASCs, in which CD56dim NK-cell impairment is observed...
January 4, 2018: Life Sciences
https://www.readbyqxmd.com/read/29167674/a-new-immunosuppressive-molecule-emodin-induces-both-cd4-foxp3-and-cd8-cd122-regulatory-t-cells-and-suppresses-murine-allograft-rejection
#6
Feifei Qiu, Huazhen Liu, Chun-Ling Liang, Golay D Nie, Zhenhua Dai
Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29159714/regulatory-effects-of-dexamethasone-on-nk-and-t-cell-immunity
#7
Liying Chen, Mikael Jondal, Konstantin Yakimchuk
Glucocorticoids (GCs) act via the intracellular glucocorticoid receptor (GR), which can regulate the expression of target genes. With regard to the immune system, GCs may affect both innate and adaptive immunity. Our study analyzed the immunoregulatory effects of dexamethasone (Dex) treatment on splenic T, Treg, NK and NKT cells by treating C57Bl6 mice with various doses of Dex. We observed that treatment with Dex decreased the number of NK cells in the spleen and suppressed their activity. In particular, the expression of both Ly49G and NKG2D receptors was decreased by Dex...
November 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29110110/changes-and-clinical-significance-of-cd8-cd122-t-cells-in-the-peripheral-blood-of-patients-with-ankylosing-spondylitis
#8
Renfang Han, Xiao Yang, Mengya Chen, Xu Zhang, Yaping Yuan, Xingxing Hu, Mengmeng Wang, Rui Liu, Yubo Ma, Jiajia Yang, Shengqian Xu, Zongwen Shuai, Shanqun Jiang, Faming Pan
The aim of our study was to explore the relationship between circulating T cells and ankylosing spondylitis (AS) and to find the role of the CD8+CD122+ T cells in the pathogenesis and progression of AS. With the method of case-control design, flow cytometry was performed to quantitatively determine the percentage of circulating CD8(+)CD122(+) T cells in peripheral blood mononuclear cells from established AS patients and age- and gender-matched healthy controls. Serum levels of inflammatory cytokines like interleukin-2, interleukin-10, interleukin-15, TGF-β1, and TNF-ɑ were detected by enzyme-linked immunosorbent assay...
November 6, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28978692/the-erm-protein-moesin-regulates-cd8-regulatory-t-cell-homeostasis-and-self-tolerance
#9
Hiroki Satooka, Daisuke Nagakubo, Tomomi Sato, Takako Hirata
The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins that link membrane proteins with actin filaments in the cell cortex and regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. Lymphocytes predominantly express two ERM members, ezrin and moesin. Mutations in the moesin gene in humans are associated with primary immunodeficiency with profound lymphopenia, and moesin-deficient mice exhibit a similar lymphopenia phenotype...
October 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28947964/chinese-medicine-ginseng-and-astragalus-granules-ameliorate-autoimmune-diabetes-by-upregulating-both-cd4-foxp3-and-cd8-cd122-pd1-regulatory-t-cells
#10
Yeshu Wang, Qingfeng Xie, Chun-Ling Liang, Qiaohuang Zeng, Zhenhua Dai
Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#11
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28855314/il-1%C3%AE-and-il-23-promote-extrathymic-commitment-of-cd27-cd122-%C3%AE-%C3%AE-t-cells-to-%C3%AE-%C3%AE-t17-cells
#12
Andreas Muschaweckh, Franziska Petermann, Thomas Korn
γδT17 cells are a subset of γδ T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. γδT17 cells are believed to arise within a narrow time window during prenatal thymic development. In agreement with this concept, we show in this study that adult Rag1-/- recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ γδT17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, γδT17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara)...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28854975/ruxolitinib-nilotinib-cotreatment-inhibits-leukemia-propagating-cells-in-philadelphia-chromosome-positive-all
#13
Yuan Kong, Yi-Lin Wu, Yang Song, Min-Min Shi, Xie-Na Cao, Hong-Yan Zhao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang
BACKGROUND: As one of the major treatment obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), relapse of Ph+ALL may result from the persistence of leukemia-propagating cells (LPCs). Research using a xenograft mouse assay recently determined that LPCs were enriched in the CD34+CD38-CD58- fraction in human Ph+ALL. Additionally, a cohort study demonstrated that Ph+ALL patients with a LPCs phenotype at diagnosis exhibited a significantly higher cumulative incidence of relapse than those with the other cell phenotypes even with uniform front-line imatinib-based therapy pre- and post-allotransplant, thus highlighting the need for novel LPCs-based therapeutic strategies...
August 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28689297/estrogen-protects-both-sexes-against-eae-by-promoting-common-regulatory-cell-subtypes-independent-of-endogenous-estrogen
#14
Hilary A Seifert, Gil Benedek, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Halina Offner
Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes...
October 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28674210/chinese-medicine-ginseng-and-astragalus-granules-ameliorate-autoimmune-diabetes-by-upregulating-both-cd4-foxp3-and-cd8-cd122-pd1-regulatory-t-cells
#15
Yeshu Wang, Qingfeng Xie, Chun-Ling Liang, Qiaohuang Zeng, Zhenhua Dai
Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652399/c-rel-and-i%C3%AE%C2%BAbns-govern-common-and-independent-steps-of-regulatory-t-cell-development-from-novel-cd122-expressing-pre-precursors
#16
Marc Schuster, Carlos Plaza-Sirvent, Anne-Marie Matthies, Ulrike Heise, Andreas Jeron, Dunja Bruder, Alexander Visekruna, Jochen Huehn, Ingo Schmitz
Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IκBNS are important regulators of Foxp3 induction in Treg precursors upon γ-chain cytokine stimulation. In c-REL/IκBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IκBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IκBNS are required for T cell effector function as well...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652304/thymic-progenitors-of-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intestinal-intraepithelial-lymphocytes-require-rasgrp1-for-development
#17
Dominic P Golec, Romy E Hoeppli, Laura M Henao Caviedes, Jillian McCann, Megan K Levings, Troy A Baldwin
Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28555090/the-distribution-of-activation-markers-and-selectins-on-peripheral-t-lymphocytes-in-preeclampsia
#18
Anna Bajnok, Maria Ivanova, János Rigó, Gergely Toldi
INTRODUCTION: Impaired maternal immune tolerance resulting in systemic inflammation plays a pivotal role in the pathogenesis of preeclampsia. Phenotypical changes of monocytes and neutrophil granulocytes have already been studied in preeclampsia, and some studies also included T lymphocyte activation markers; however, the results are controversial and a comprehensive analysis of activation markers is lacking. The characteristics of cellular adhesion molecules in preeclampsia are yet to be described...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28507024/cutting-edge-differential-fine-tuning-of-il-2-and-il-15-dependent-functions-by-targeting-their-common-il-2-15r%C3%AE-%C3%AE-c-receptor
#19
Dihia Meghnem, Sébastien Morisseau, Marie Frutoso, Kilian Trillet, Mike Maillasson, Isabelle Barbieux, Sarah Khaddage, Isabelle Leray, Markus Hildinger, Agnès Quéméner, Yannick Jacques, Erwan Mortier
Interleukin 2 and IL-15 are two closely related cytokines, displaying important functions in the immune system. They share the heterodimeric CD122/CD132 receptor to deliver their signals within target cells. Their specificity of action is conferred by their α receptor chains, IL-2Rα and IL-15Rα. By combining an increased affinity for CD122 and an impaired recruitment of CD132, we have generated an original molecule named IL-2Rβ/γ (CD122/CD132) inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL-15- and IL-2-dependent functions of primary cells, including CD8 T and NK cells, in vitro and in vivo...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#20
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
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