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https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#5
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28708784/apoptotic-diminution-of-immature-single-and-double-positive-thymocyte-subpopulations-contributes-to-thymus-involution-during-murine-polymicrobial-sepsis
#6
Christoph Netzer, Tilo Knape, Laura Kuchler, Andreas Weigert, Kai Zacharowski, Waltraud Pfeilschifter, Gregory Sempowski, Michael J Parnham, Bernhard Brüne, Andreas von Knethen
To generate and maintain functional T-cell receptor diversity, thymocyte development is tightly organized. Errors in this process may have dramatic consequences, provoking, for example, autoimmune diseases. Probably for this reason, the thymus reacts to septic stress with involution, decreasing the numbers of thymocytes. Because it is still unclear which thymocyte subpopulation contributes to thymus involution and whether thymocyte emigration is altered, we were interested to clarify this question in detail...
August 2017: Shock
https://www.readbyqxmd.com/read/28708266/belatacept-conversion-in-an-hiv-positive-kidney-transplant-recipient-following-anti-thymocyte-globulin-induction
#7
Samatha A Kuten, Samir J Patel, Ashvin Baru, A Osama Gaber, Rustin D Crutchley, Venkataraman Ramanathan, Richard J Knight
Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction...
July 14, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28705902/long-term-risk-of-cancer-development-in-adult-patients-with-idiopathic-aplastic-anemia-after-treatment-with-anti-thymocyte-globulin
#8
Joost Gk van der Hem, Liesbeth C de Wreede, Anneke Brand, Hendrik Veelken, Jh Frederik Falkenburg, Constantijn Jm Halkes
No abstract text is available yet for this article.
July 13, 2017: Haematologica
https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#9
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28698642/progressive-changes-in-cxcr4-expression-that-define-thymocyte-positive-selection-are-dispensable-for-both-innate-and-conventional-%C3%AE-%C3%AE-t-cell-development
#10
Beth Lucas, Andrea J White, Sonia M Parnell, Peter M Henley, William E Jenkinson, Graham Anderson
The ordered migration of immature thymocytes through thymic microenvironments generates both adaptive MHC restricted αβT-cells and innate CD1d-restricted iNKT-cells. While several chemokine receptors and ligands control multiple stages of this process, their involvement during early thymocyte development often precludes direct analysis of potential roles during later developmental stages. For example, because of early lethality of CXCR4(-/-) mice, and stage-specific requirements for CXCR4 in thymus colonisation and pre-TCR mediated selection, its role in thymic positive selection is unclear...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697966/themis-two-models-different-thresholds
#11
REVIEW
Seeyoung Choi, Richard Cornall, Renaud Lesourne, Paul E Love
THEMIS, a recently identified T-lineage-restricted protein, is the founding member of a large metazoan protein family. Gene inactivation studies have revealed a critical requirement for THEMIS during thymocyte positive selection, implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR), but the mechanistic underpinnings of THEMIS function have remained elusive. A previous model posited that THEMIS prevents thymocytes from inappropriately crossing the positive/negative selection threshold by dampening TCR signaling...
July 8, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28694386/a-type-2-cytokine-axis-for-thymus-emigration
#12
Andrea J White, Song Baik, Sonia M Parnell, Amanda M Holland, Frank Brombacher, William E Jenkinson, Graham Anderson
In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants...
July 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28677744/simvastatin-ameliorates-ionizing-radiation-induced-apoptosis-in-the-thymus-by-activating-the-akt-sirtuin-1-pathway-in-mice
#13
Hong Yang, Fei Huang, Yulong Tao, Xinbin Zhao, Lina Liao, Xia Tao
Simvastatin is a HMG-CoA reductase inhibitor widely used to lower plasma cholesterol and to protect against cardiovascular risk factors. The aim of this study was to investigate whether simvastatin attenuates ionizing radiation-induced damage in the mouse thymus and to elucidate the possible mechanisms invovled. For this purpose, male C57BL/6J mice aged 6 weeks were used and exposed to 4 Gy 60Co γ-radiation with or without simvastatin (20 mg/kg/day, for 14 days). Apoptosis was determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay or transmission electron microscopy (TEM) examination...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#14
REVIEW
Marieke van der Zwan, Carla C Baan, Teun van Gelder, Dennis A Hesselink
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials...
July 1, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28668491/validation-of-the-hematopoietic-cell-transplantation-specific-comorbidity-index-in-non-myeloablative-allogeneic-stem-cell-transplantation
#15
Muthu Veeraputhiran, Lingyao Yang, Vandana Sundaram, Sally Arai, Robert Lowsky, David Miklos, Everett Meyer, Lori Muffly, Robert Negrin, Andrew Rezvani, Judith Shizuru, Wen Kai Weng, Laura Johnston
The Hematopoietic cell transplant-comorbidity index (HCT-CI) has been extensively studied in myeloablative (MA) and reduced intensity conditioning (RIC) regimens with less available data regarding the validity of HCT-CI in non-myeloablative (NMA) allogeneic transplant. We conducted a retrospective analysis to evaluate the association between HCT-CI and non-relapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the Total Lymphoid Irradiation and Anti-thymocyte Globulin (TLI/ATG) NMA transplant preparative regimen...
June 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28659354/structural-and-mechanistic-implications-of-rearrangement-frequencies-within-human-tcrbv-genes
#16
Maryam B Yassai, Wendy Demos, Jack Gorski
The T cell repertoire is a function of thymic V(D)J rearrangement and of peripheral selection. The mature repertoire embodies TCR sequences that are important for survival and can identify important structural aspects of the TCR. Analysis of the circulating TCRBV19 CD8 T cell repertoire showed that a majority of NDN-encoded CDR3 amino acid motifs start at CDR3 position four, well within the V region. Rearrangement at this position indicates that the DNA hairpin loop is not opened at the position adjacent to the recombination signal sequence, but rather is trimmed back three or more bases...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28659353/alterations-in-the-thymic-selection-threshold-skew-the-self-reactivity-of-the-tcr-repertoire-in-neonates
#17
Mengqi Dong, Patricio Artusa, Stephanie A Kelly, Marilaine Fournier, Troy A Baldwin, Judith N Mandl, Heather J Melichar
Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652564/risk-factors-for-graft-versus-host-disease-after-transplantation-of-hematopoietic-stem-cells-from-unrelated-donors-in-the-china-marrow-donor-program
#18
Fan Yang, Daopei Lu, Yu Hu, Xiaojun Huang, He Huang, Jing Chen, Depei Wu, Jianmin Wang, Chun Wang, Mingzhe Han, Hu Chen
BACKGROUND We identified risk factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) in recipients after hematopoietic stem cell transplantation (HSCT) from unrelated donors in the China Marrow Donor Program (CMDP). MATERIAL AND METHODS We analyzed follow-up clinical information from 1824 patients who underwent HSCT between 2001 and 2010. RESULTS The incidence of aGVHD and cGVHD after transplantation was 49.29% and 27.3%, respectively. aGVHD incidence decreased as HLA matching increased (p<0...
June 27, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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
#19
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...
June 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28652130/tal1-as-a-master-oncogenic-transcription-factor-in-t-cell-acute-lymphoblastic-leukemia
#20
REVIEW
Takaomi Sanda, Wei Zhong Leong
In hematopoietic cell development, the transcriptional program is strictly regulated in a lineage- and stage-specific manner that requires a number of transcription factors to work in a cascade or in a loop, in addition to interactions with nonhematopoietic cells in the microenvironment. Disruption of the transcriptional program alters the cellular state and may predispose cells to the acquisition of genetic abnormalities. Early studies have shown that proteins that promote cell differentiation often serve as tumor suppressors, whereas inhibitors of those proteins act as oncogenes in the context of acute leukemia...
June 24, 2017: Experimental Hematology
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