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https://www.readbyqxmd.com/read/28815344/long-term-survival-after-hematopoietic-stem-cell-transplantation-for-complete-stat1-deficiency
#1
Samuele Naviglio, Elena Soncini, Donatella Vairo, Arnalda Lanfranchi, Raffaele Badolato, Fulvio Porta
PURPOSE: Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT)...
August 16, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28801656/comprehensive-mirna-expression-profiling-in-human-t-cell-acute-lymphoblastic-leukemia-by-small-rna-sequencing
#2
Annelynn Wallaert, Wouter Van Loocke, Lucie Hernandez, Tom Taghon, Frank Speleman, Pieter Van Vlierberghe
T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800929/directing-t-cell-fate-how-thymic-antigen-presenting-cells-coordinate-thymocyte-selection
#3
REVIEW
Elise R Breed, S Thera Lee, Kristin A Hogquist
The development of a self-tolerant and effective T cell receptor repertoire is dependent on interactions coordinated by various antigen presenting cells (APC) within the thymus. T cell receptor-self-peptide-MHC interactions are essential for determining T cell fate, however different cytokine and co-stimulatory signals provided by the diverse APCs within the thymus are also critical. Here, we outline the different localization and functional capabilities of thymic APCs. We also discuss how these distinct APCs work collectively to facilitate the establishment of a diverse T cell receptor repertoire that is tolerant to an array of different self-antigens...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28797029/successful-use-of-equine-anti-thymocyte-globulin-atgam-for-fulminant-myocarditis-secondary-to-nivolumab-therapy
#4
Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill, Andrew Haydon
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality. METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28793897/aqueous-extract-of-phragmitis-rhizoma-ameliorates-myelotoxicity-of-docetaxel-in-vitro-and-in-vivo
#5
Jinhee Kim, You Jin Lee, Young Ah Kim, Eun-Sang Cho, Eunna Huh, Ok-Sun Bang, No Soo Kim
BACKGROUND: A variety of anticancer chemotherapeutics induce adverse side effects including myelotoxicity. Dried roots of Phragmites communis Trinius, Phragmitis rhizoma, have been clinically used in traditional folk medicine to relieve various symptoms like fever. In this study, we evaluated the protective effect of the aqueous extract of Phragmitis rhizoma (EPR) against docetaxel-induced myelotoxicity in vitro and in vivo. METHODS: The in vitro myelo-protective effect of EPR was evaluated using the colony forming unit (CFU) assay with hematopoietic progenitor cells...
August 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28783686/the-checkpoint-for-agonist-selection-precedes-conventional-selection-in-human-thymus
#6
Greet Verstichel, David Vermijlen, Liesbet Martens, Glenn Goetgeluk, Margreet Brouwer, Nicolas Thiault, Yasmine Van Caeneghem, Stijn De Munter, Karin Weening, Sarah Bonte, Georges Leclercq, Tom Taghon, Tessa Kerre, Yvan Saeys, Jo Van Dorpe, Hilde Cheroutre, Bart Vandekerckhove
The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist-selected lineages also relies on strong TCR signaling. How thymocytes discriminate between these opposite outcomes remains elusive. Here, we identified a human agonist-selected PD-1(+) CD8αα(+) subset of mature CD8αβ(+) T cells that displays an effector phenotype associated with agonist selection. TCR stimulation of immature post-β-selection thymocyte blasts specifically gives rise to this innate subset and fixes early T cell receptor alpha variable (TRAV) and T cell receptor alpha joining (TRAJ) rearrangements in the TCR repertoire...
February 24, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783143/unrelated-cord-blood-transplantation-in-aplastic-anemia-is-anti-thymocyte-globulin-indispensable-for-conditioning
#7
K Kudo, H Muramatsu, A Narita, N Yoshida, R Kobayashi, H Yabe, M Endo, M Inoue, J Hara, S Kounami, J Inagaki, Y Hashii, K Kato, K Tabuchi, S Kojima
No abstract text is available yet for this article.
August 7, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28769045/arsenic-exposure-impels-cd4-commitment-in-thymus-and-suppress-t-cell-cytokine-secretion-by-increasing-regulatory-t-cells
#8
Ruchi Gera, Vikas Singh, Sumonto Mitra, Anuj Kumar Sharma, Alok Singh, Arunava Dasgupta, Dhirendra Singh, Mahadeo Kumar, Pankaj Jagdale, Satyakam Patnaik, Debabrata Ghosh
Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767666/mismatch-repair-deficient-hematopoietic-stem-cells-are-preleukemic-stem-cells
#9
Yulan Qing, Stanton L Gerson
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus...
2017: PloS One
https://www.readbyqxmd.com/read/28754820/an-integrative-scoring-system-for-survival-prediction-following-umbilical-cord-blood-transplantation-in-acute-leukemia
#10
Roni Shouval, Annalisa Ruggeri, Myriam Labopin, Mohamad Mohty, Guillermo Sanz, Gérard Michel, Jurgen Kuball, Patrice Chevallier, Amal Al-Seraihy, Noel-Jean Milpied, Cristina Díaz Heredia, William Arcese, Didier Blaise, Vanderson Rocha, Joshua Fein, Ron Unger, Frederic Baron, Bader Peter, Eliane Gluckman, Arnon Nagler
Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free survival (LFS) at 2-years following UCBT in AL patients. <p>Experimental design: The study cohort included 3,140 pediatric and adult AL UCBT patients from the European Society of Blood and Marrow Transplantation and Eurocord registries...
July 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28745324/a-committed-postselection-precursor-to-natural-tcr%C3%AE-%C3%AE-intraepithelial-lymphocytes
#11
Christoph S N Klose, Jonas F Hummel, Lena Faller, Yannick d'Hargues, Karolina Ebert, Yakup Tanriver
The intestine is a major immune organ with several specialized lymphoid structures and immune cells. Among these are thymus-derived natural intraepithelial lymphocytes (IELs) that lack expression of the classical co-receptors CD4 or CD8αβ (double negative (DN)). Natural IELs are both αβ(+) and γδ(+) T cells that play important roles in the maintenance of the epithelial barrier at steady state and during inflammation. The transcription factor T-bet is essential for the peripheral development of natural IELs, but its role during thymic development has remained less clear...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#12
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28735895/a-phosphosite-within-the-sh2-domain-of-lck-regulates-its-activation-by-cd45
#13
Adam H Courtney, Jeanine F Amacher, Theresa A Kadlecek, Marianne N Mollenauer, Byron B Au-Yeung, John Kuriyan, Arthur Weiss
The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28733484/cutting-edge-cd3-itam-diversity-is-required-for-optimal-tcr-signaling-and-thymocyte-development
#14
Matthew L Bettini, Po-Chein Chou, Clifford S Guy, Thomas Lee, Kate M Vignali, Dario A A Vignali
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28732720/impact-on-mid-term-kidney-graft-outcomes-of-pretransplant-anti-hla-antibodies-detected-by-solid-phase-assays-do-donor-specific-antibodies-tell-the-whole-story
#15
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0...
July 19, 2017: Human Immunology
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#16
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#17
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28718381/histological-and-immunohistochemical-characterization-of-the-similarity-and-difference-between-ovarian-endometriomas-and-deep-infiltrating-endometriosis
#18
Xishi Liu, Qi Zhang, Sun-Wei Guo
Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#19
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
BACKGROUND: Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. METHODS: Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28716402/the-role-of-low-dose-anti-thymocyte-globulin-as-standard-prophylaxis-in-mismatched-and-matched-unrelated-hematopoietic-peripheral-stem-cell-transplantation-for-hematologic-malignancies
#20
Ioanna Sakellari, Ioannis Batsis, Zoi Bousiou, Despina Mallouri, Varnavas Constantinou, Eleni Gavriilaki, Christos Smias, Evangelia Yannaki, Panayotis Kaloyannidis, Giorgos Papaioannou, Niki Stavroyianni, Antonia Syrigou, Damianos Sotiropoulos, Asimina Fylaktou, Aliki Tsompanakou, Riad Saloum, Achilles Anagnostopoulos
INTRODUCTION: Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD). PATIENTS AND METHODS: In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors...
June 29, 2017: Clinical Lymphoma, Myeloma & Leukemia
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