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https://www.readbyqxmd.com/read/28548945/soluble-antigens-from-the-neurotropic-pathogen-angiostrongylus-cantonensis-directly-induce-thymus-atrophy-in-a-mouse-model
#1
Zhen Liu, Dong-Ming Su, Zi-Long Yu, Feng Wu, Rui-Feng Liu, Shi-Qi Luo, Zhi-Yue Lv, Xin Zeng, Xi Sun, Zhong-Dao Wu
The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546567/thymic-homing-of-activated-cd4-t-cells-induces-degeneration-of-the-thymic-epithelium-through-excessive-rank-signaling
#2
Chen Yin, Xiao-Yan Pei, Hui Shen, Ya-Nan Gao, Xiu-Yuan Sun, Wei Wang, Qing Ge, Yu Zhang
Activated T cells have been shown to be able to recirculate into the thymus from the periphery. The present study was aimed to elucidate the functional consequences of thymic homing of activated T cells upon developing thymocytes and thymic epithelial cells (TEC). In the presence of activated T cells, especially CD4(+) T cells, T cell development was found to be inhibited in thymic organ cultures with markedly reduced cellularity. Thymic transplantation demonstrated that the inhibitory effect was most likely due to a defective microenvironment...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539428/cutting-edge-dual-tcr%C3%AE-expression-poses-an-autoimmune-hazard-by-limiting-regulatory-t-cell-generation
#3
Nathaniel J Schuldt, Jennifer L Auger, Justin A Spanier, Tijana Martinov, Elise R Breed, Brian T Fife, Kristin A Hogquist, Bryce A Binstadt
Despite accounting for 10-30% of the T cell population in mice and humans, the role of dual TCR-expressing T cells in immunity remains poorly understood. It has been hypothesized that dual TCR T cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection. We revisited this hypothesis using the NOD murine model of type 1 diabetes. We bred NOD mice hemizygous at both TCRα and β (TCRα(+/-) β(+/-)) loci, rendering them incapable of producing dual TCR T cells. We found that the lack of dual TCRα expression skewed the insulin-specific thymocyte population toward greater regulatory T (Treg) cell commitment, resulting in a more tolerogenic Treg to conventional T cell ratio and protection from diabetes...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28536901/increased-epithelial-free-areas-in-thymuses-with-altered-ephb-mediated-thymocyte-thymic-epithelial-cell-interactions
#4
Javier García-Ceca, Sara Montero-Herradón, David Alfaro, Agustín G Zapata
Epithelial-free areas, present in both thymic cortex and medulla, have been studied in WT and EphB-deficient mice that have important alterations in the development of thymic epithelium due to the lack of proper thymocyte-thymic epithelial cell interactions. In both WT and mutant thymuses, the number and size of epithelial-free areas are significantly larger in the medulla than in the cortex. The two parameters show a reverse correlation: low numbers of these areas course with large epithelial-free areas and vice versa...
May 24, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#5
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#6
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28515359/t-cell-progenitor-therapy-facilitated-thymopoiesis-depends-upon-thymic-input-and-continued-thymic-microenvironment-interaction
#7
Michelle J Smith, Dawn K Reichenbach, Sarah L Parker, Megan J Riddle, Jason Mitchell, Kevin C Osum, Mahmood Mohtashami, Heather E Stefanski, Brian T Fife, Avinash Bhandoola, Kristin A Hogquist, Georg A Holländer, Juan Carlos Zúñiga-Pflücker, Jakub Tolar, Bruce R Blazar
Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28508570/a-new-transcript-in-the-tcrb-locus-unveils-the-human-ortholog-of-the-mouse-pre-d%C3%A3-1-promoter
#8
Bernard Lethé, Sylvia Snauwaert, Orian Bricard, David Schröder, Tiphanie Gomard, Gérald Hames, Catherine Muller, Christophe Lurquin, Emilie Gauthy, Ahmed Essaghir, Bart Vandekerckhove, Pierre G Coulie
INTRODUCTION: While most transcripts arising from the human T Cell Receptor locus reflect fully rearranged genes, several germline transcripts have been identified. We describe a new germline transcript arising from the human TCRB locus. METHODS: cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript. RESULTS: The new germline transcript encoded by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1 (X1), spliced with the first exon of gene segments Cß1 or Cß2...
May 15, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28494867/essential-roles-of-satb1-in-specifying-t-lymphocyte-subsets
#9
Kiyokazu Kakugawa, Satoshi Kojo, Hirokazu Tanaka, Wooseok Seo, Takaho A Endo, Yohko Kitagawa, Sawako Muroi, Mari Tenno, Nighat Yasmin, Yoshinori Kohwi, Shimon Sakaguchi, Terumi Kowhi-Shigematsu, Ichiro Taniuchi
T cell receptor (TCR) signaling by MHC class I and II induces thymocytes to acquire cytotoxic and helper fates via the induction of Runx3 and ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. Here, we show that, in post-selection thymocytes, a genome organizer, SATB1, activates genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8, and Treg factor Foxp3, via regulating enhancers in these genes in a locus-specific manner...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28494186/small-interference-itga6-gene-targeting-in-the-human-thymic-epithelium-differentially-regulates-the-expression-of-immunological-synapse-related-genes
#10
Daiane Cristina F Golbert, Eliane Santana-Van-Vliet, Marcelo Ribeiro-Alves, Marbella Maria B da Fonsêca, Ailin Lepletier, Daniella Arêas Mendes-da-Cruz, Guilherme Loss, Vinícius Cotta-de-Almeida, Ana Tereza R Vasconcelos, Wilson Savino
The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ...
May 11, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28489305/prolonged-survival-following-pig-to-primate-liver-xenotransplantation-utilizing-exogenous-coagulation-factors-and-co-stimulation-blockade
#11
J A Shah, M S Patel, N Elias, N Navarro-Alvarez, I Rosales, R A Wilkinson, N J Louras, M Hertl, J A Fishman, R B Colvin, A B Cosimi, J F Markmann, D H Sachs, P A Vagefi
Since the first attempt in 1968, survival following pig-to-primate liver xenotransplantation (LXT) has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous post-transplant infusion of human prothrombin concentrate complex and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone and co-stimulation blockade (belatacept, n=3 or anti-CD40mAb, n=1) to extend survival. Baboon #1 remained well until POD25 when euthanasia was required due to cholestasis and plantar ulcers...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28484270/risk-factors-for-pneumocystis-jirovecii-pneumonia-pjp-in-kidney-transplantation-recipients
#12
Su Hwan Lee, Kyu Ha Huh, Dong Jin Joo, Myoung Soo Kim, Soon Il Kim, Juhan Lee, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Yu Seun Kim, Song Yee Kim
Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised patients. The aim of this study was to evaluate risk factors for PJP in kidney transplantation recipients. We conducted a retrospective analysis of patient data from 500 consecutive kidney transplants performed at Severance Hospital between April 2011 and April 2014. Eighteen kidney transplantation recipients (3.6%) were diagnosed with PJP. In the univariate analysis, acute graft rejection, CMV infection, use of medication for diabetes mellitus, and lowest lymphocyte count were associated with PJP...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28473904/from-chronic-immune-thrombocytopenia-to-severe-aplastic-anemia-recent-insights-into-the-evolution-of-eltrombopag
#13
REVIEW
Harinder Gill, Raymond S M Wong, Yok-Lam Kwong
Thrombopoietin (TPO) is the most potent cytokine stimulating thrombopoiesis. Therapy with exogenous TPO is limited by the formation of antibodies cross-reacting with endogenous TPO. Mimetics of TPO are compounds with no antigenic similarity to TPO. Eltrombopag is an orally-active nonpeptide small molecule that binds to the transmembrane portion of the TPO receptor MPL. Initial trials of eltrombopag have centered on immune thrombocytopenia (ITP), which is due to both increased destruction and decreased production of platelets...
May 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28472378/efflux-transporters-regulate-arsenite-induced-genotoxicity-in-double-negative-and-double-positive-t-cells
#14
Huan Xu, Sebastian Medina, Fredine T Lauer, Christelle Douillet, Ke Jian Liu, Laurie G Hudson, Miroslav Stýblo, Lauren M Aleksunes, Scott W Burchiel
Arsenite (As+3) exposure is known to cause immunotoxicity in human and animal models. Our previous studies demonstrated that As+3 at 50 to 500 nM concentrations induced both genotoxicity and non-genotoxicity in mouse thymus cells. Developing T cells at CD4-CD8- double negative (DN) stage, the first stage after early T cells are transported from bone marrow to thymus, were found to be more sensitive to As+3 toxicity than the T cells at CD4+CD8+ double positive (DP) stage in vitro. Induction of Mdr1 (Abcb1) and Mrp1 (Abcc1), two multidrug resistance transporters and exporters of As+3, was associated with the reversal of As+3-induced double strand breaks and DNA damage...
April 29, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28471480/microrna-142-controls-thymocyte-proliferation
#15
Alexander Mildner, Elik Chapnik, Diana Varol, Tegest Aychek, Nardi Lampl, Natalia Rivkin, Anita Bringmann, Franziska Paul, Sigalit Boura-Halfon, Yifat Segal Hayoun, Zohar Barnett-Itzhaki, Ido Amit, Eran Hornstein, Steffen Jung
T-cell development is a spatially and temporally regulated process, orchestrated by well-defined contributions of transcription factors and cytokines. Here, we identify the non-coding RNA miR-142 as an additional regulatory layer within murine thymocyte development and proliferation. MiR-142 deficiency impairs the expression of cell cycle-promoting genes in mature mouse thymocytes and early progenitors, accompanied with increased levels of Cyclin-dependent kinase inhibitor 1B (Cdkn1b, also known as p27(Kip1) )...
May 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28468970/concomitant-disruption-of-cd4-and-cd8-genes-facilitates-the-development-of-double-negative-%C3%AE-%C3%AE-tcr-peripheral-t-cells-that-respond-robustly-to-staphylococcal-superantigen
#16
Vaidehi R Chowdhary, Ashton Krogman, Ashenafi Y Tilahun, Mariam P Alexander, Chella S David, Govindarajan Rajagopalan
Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated CD4 and CD8 genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors...
May 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28462532/cell-death-and-thymic-tolerance
#17
REVIEW
Stephen R Daley, Charis Teh, Daniel Y Hu, Andreas Strasser, Daniel H D Gray
The differentiation of hematopoietic precursors into the many functionally distinct T-cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T-cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T-cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28455312/administration-of-rankl-boosts-thymic-regeneration-upon-bone-marrow-transplantation
#18
Noella Lopes, Hortense Vachon, Julien Marie, Magali Irla
Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4(+) thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration...
April 28, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28447098/application-of-natural-language-processing-and-network-analysis-techniques-to-post-market-reports-for-the-evaluation-of-dose-related-anti-thymocyte-globulin-safety-patterns
#19
Taxiarchis Botsis, Matthew Foster, Nina Arya, Kory Kreimeyer, Abhishek Pandey, Deepa Arya
OBJECTIVE: To evaluate the feasibility of automated dose and adverse event information retrieval in supporting the identification of safety patterns. METHODS: We extracted all rabbit Anti-Thymocyte Globulin (rATG) reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) from the product's initial licensure in April 16, 1984 through February 8, 2016. We processed the narratives using the Medication Extraction (MedEx) and the Event-based Text-mining of Health Electronic Records (ETHER) systems and retrieved the appropriate medication, clinical, and temporal information...
April 26, 2017: Applied Clinical Informatics
https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#20
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
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