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https://www.readbyqxmd.com/read/27915416/opposing-effects-on-the-cell-cycle-of-t-lymphocytes-by-fbxo7-via-cdk6-and-p27
#1
Shachi P Patel, Suzanne J Randle, Sarah Gibbs, Anne Cooke, Heike Laman
G1 phase cell cycle proteins, such as cyclin-dependent kinase 6 (Cdk6) and its activating partners, the D-type cyclins, are important regulators of T-cell development and function. An F-box protein, called F-box only protein 7 (Fbxo7), acts as a cell cycle regulator by enhancing cyclin D-Cdk6 complex formation and stabilising levels of p27, a cyclin-dependent kinase inhibitor. We generated a murine model of reduced Fbxo7 expression to test its physiological role in multiple tissues and found that these mice displayed a pronounced thymic hypoplasia...
December 3, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27905258/hla-mismatched-haploidentical-transplantation-using-low-dose-anti-thymocyte-globulin-atg-thymoglobulin
#2
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Yoshinobu Kanda
Objectives To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT). Methods Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate. Results The median age of the patients was 33 years...
December 1, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#3
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899442/early-generated-b1-b-cells-with-restricted-bcrs-become-chronic-lymphocytic-leukemia-with-continued-c-myc-and-low-bmf-expression
#4
Kyoko Hayakawa, Anthony M Formica, Joni Brill-Dashoff, Susan A Shinton, Daiju Ichikawa, Yan Zhou, Herbert C Morse, Richard R Hardy
In mice, generation of autoreactive CD5(+) B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from Eμ-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27899357/a-phase-iii-randomized-trial-comparing-inolimomab-vs-usual-care-in-steroid-resistant-acute-gvhd
#5
Gérard Socié, Stéphane Vigouroux, Ibrahim Yakoub-Agha, Jacques-Olivier Bay, Sabine Fürst, Karin Bilger, Felipe Suarez, Mauricette Michallet, Dominique Bron, Philippe Gard, Zakaria Medeghri, Philippe Lehert, Chinglin Lai, Tim Corn, Jean-Paul Vernant
Treatment of steroid resistant (SR) aGVHD remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase II trials. This phase III randomized, open-label, multicenter compared Inolimomab vs. usual care in adult patients with steroid-refractory aGvHD. Patients were randomized to treatment with Inolimomab or usual care [control group were all treated with Anti Thymocyte Globulin (ATG)]. The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27895179/thymic-dendritic-cell-subsets-display-distinct-efficiencies-and-mechanisms-of-intercellular-mhc-transfer
#6
Charles J Kroger, Nicholas A Spidale, Bo Wang, Roland Tisch
Thymic dendritic cells (DC) delete self-antigen-specific thymocytes, and drive development of Foxp3-expressing immunoregulatory T cells. Unlike medullary thymic epithelial cells, which express and present peripheral self-antigen, DC must acquire self-antigen to mediate thymic negative selection. One such mechanism entails the transfer of surface MHC-self peptide complexes from medullary thymic epithelial cells to thymic DC. Despite the importance of thymic DC cross-dressing in negative selection, the factors that regulate the process and the capacity of different thymic DC subsets to acquire MHC and stimulate thymocytes are poorly understood...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#7
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
November 26, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27877175/thymocytes-in-lyve1-cre-s1pr1-f-f-mice-accumulate-in-the-thymus-due-to-cell-intrinsic-loss-of-sphingosine-1-phosphate-receptor-expression
#8
Akira Takeda, Mohammad Shahadat Hossain, Pia Rantakari, Szandor Simmons, Naoko Sasaki, Marko Salmi, Sirpa Jalkanen, Masayuki Miyasaka
T cell emigration from the thymus is essential for immunological homeostasis. While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to promote thymocyte egress via the S1P receptor, S1PR1, the significance of S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains unclear. To address this issue, we developed conditional knockout mice (Lyve1-CRE/S1pr1(f/f) mice) in which S1pr1 was selectively targeted in cells expressing the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were significantly reduced in secondary lymphoid tissues, and CD62L(+) mature CD4 and CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo thymus egress...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#9
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27864993/thyrotropin-alters-t-cell-development-in-the-thymus-in-subclinical-hypothyroidism-mouse-model
#10
Kunpeng Wu, Meng Zhao, Chunyan Ma, Haiqing Zhang, Xiaojing Liu, Lingyan Zhou, Jiajun Zhao, Ling Gao, Dan Wang
Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, were used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls...
November 16, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27864278/integrative-analysis-for-the-role-of-long-non-coding-rnas-in-radiation-induced-mouse-thymocytes-responses
#11
Hui Gao, Zhuo Dong, Wei Wei, Lihong Shao, Linlin Jin, Yahui Lv, Gang Zhao, Shunzi Jin
Long non-coding RNAs (lncRNAs) are a critical class of regulatory molecules involved in a variety of biological functions; however, their role in immune cells response to radiation is unknown. Therefore, in this study we used integrative analysis to determine the expression profile of lncRNAs in mouse thymocytes and the potential functions of lncRNAs in response to radiation. Microarray data profiling indicated that 53 lncRNAs (36 up-regulated and 17 down-regulated) and 74 coding genes (39 up-regulated and 35 down-regulated) were highly differentially expressed in the high dose radiation (HDR) group compared with the control group...
November 17, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27861499/maternal-filarial-infection-influences-the-development-of-regulatory-t-cells-in-children-from-infancy-to-early-childhood
#12
Madhusmita Bal, Manoranjan Ranjit, K Gopinath Achary, Ashok K Satapathy
BACKGROUND: Children born from filarial infected mothers are comparatively more susceptible to filarial infection than the children born to uninfected mothers. But the mechanism of such increased susceptibility to infection in early childhood is not exactly known. Several studies have shown the association of active filarial infection with T cell hypo-responsiveness which is mediated by regulatory T cells (Tregs). Since the Tregs develop in the thymus from CD4+ CD25hi thymocytes at an early stage of the human fetus, it can be hypothesized that the maternal infection during pregnancy affects the development of Tregs in children at birth as well as early childhood...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27857075/linear-ubiquitin-chain-assembly-complex-coordinates-late-thymic-t-cell-differentiation-and-regulatory-t-cell-homeostasis
#13
Charis E Teh, Najoua Lalaoui, Reema Jain, Antonia N Policheni, Melanie Heinlein, Silvia Alvarez-Diaz, Julie M Sheridan, Eva Rieser, Stefanie Deuser, Maurice Darding, Hui-Fern Koay, Yifang Hu, Fiona Kupresanin, Lorraine A O'Reilly, Dale I Godfrey, Gordon K Smyth, Philippe Bouillet, Andreas Strasser, Henning Walczak, John Silke, Daniel H D Gray
The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3(+) regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation...
November 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27852740/temporal-expression-of-bim-limits-the-development-of-agonist-selected-thymocytes-and-skews-their-tcr%C3%AE-repertoire
#14
Kun-Po Li, Anke Fähnrich, Eron Roy, Carla M Cuda, H Leighton Grimes, Harris R Perlman, Kathrin Kalies, David A Hildeman
CD8αα TCRαβ(+) intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell-specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27837196/abnormal-thymic-maturation-and-lymphoproliferation-in-mrl-faslpr-lpr-mice-can-be-partially-reversed-by-synthetic-oligonucleotides-implications-for-systemic-lupus-erythematosus-and-autoimmune-lymphoproliferative-syndrome
#15
R F Ashman, N Singh, P S Lenert
MRL-Fas (lpr/lpr) mice represent an excellent animal model for studying non-malignant lymphoproliferation, regeneration and systemic autoimmunity. Retro-transposon insertion into the second intron of the pro-apoptotic Fas gene appears to be responsible for both lymphoproliferation and autoimmunity, while other genes are more likely to contribute to the regenerative healing characteristic of this mouse strain. Previous studies have shown that neonatal thymectomy can halt the development of abnormal lymphoproliferation...
November 10, 2016: Lupus
https://www.readbyqxmd.com/read/27834348/erratum-thymic-dcs-derived-il-27-regulates-the-final-maturation-of-cd4-sp-thymocytes
#16
Hui Tang, Jie Zhang, Xiuyuan Sun, Xiaoping Qian, Yu Zhang, Rong Jin
No abstract text is available yet for this article.
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27833166/soluble-%C3%AE-c-cytokine-receptor-suppresses-il-15-signaling-and-impairs-inkt-cell-development-in-the-thymus
#17
Joo-Young Park, Yuna Jo, Eunhee Ko, Megan A Luckey, Yoo Kyoung Park, Se-Ho Park, Jung-Hyun Park, Changwan Hong
The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4(+)CD8(+) thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27829155/p53-activity-results-in-dna-replication-fork-processivity
#18
Ina Klusmann, Sabrina Rodewald, Leonie Müller, Mascha Friedrich, Magdalena Wienken, Yizhu Li, Ramona Schulz-Heddergott, Matthias Dobbelstein
p53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. We report that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This is observed in tumor-derived U2OS cells but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion and in freshly isolated thymocytes from mice with differential p53 status. Mdm2, a p53-inducible gene product, similarly supports DNA replication even in p53-deficient cells, suggesting that sustained Mdm2-expression is at least one of the mechanisms allowing p53 to prevent replicative stress...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27826566/variations-in-mrna-and-protein-levels-of-ikaros-family-members-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#19
Julie L Mitchell, Thomas M Yankee
BACKGROUND: Pediatric T cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease in which the cells share phenotypic characteristics with normal human thymocytes. The Ikaros family of transcription factors includes five members that are required for normal T cell development and are implicated in leukemogenesis. The goal of this work was to correlate the pattern of expression of Ikaros family members with the phenotype of the T-ALL cells. METHODS: We obtained twenty-four samples from pediatric T-ALL patients and used multi-parameter flow cytometry to characterize each sample, comparing the phenotype of the leukemic cells with normal human thymocytes...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27825298/the-ut-family-of-mhc-class-i-loci-unique-to-non-eutherian-mammals-has-limited-polymorphism-and-tissue-specific-patterns-of-expression-in-the-opossum
#20
Katina V Krasnec, Anthony T Papenfuss, Robert D Miller
BACKGROUND: The Major Histocompatibility Complex (MHC) class I family of genes encode for molecules that have well-conserved structures, but have evolved to perform diverse functions. The availability of the gray, short-tailed opossum, Monodelphis domestica whole genome sequence has allowed for analysis of MHC class I gene content in this marsupial. Utilization of a novel method to search for MHC related domain structures revealed a previously unknown family of MHC class I-related genes...
November 8, 2016: BMC Immunology
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