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https://www.readbyqxmd.com/read/28411578/differential-effects-of-low-dose-fludarabine-or-5-fluorouracil-on-the-tumor-growth-and-myeloid-derived-immunosuppression-status-of-tumor-bearing-mice
#1
Manuchehr Abedi-Valugerdi, Wenyi Zheng, Fadwa Benkessou, Ying Zhao, Moustapha Hassan
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a key role in the suppression of the innate and adaptive immunity. Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to reduce the tumor size by depleting MDSCs. Here, we asked whether the purine analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma model, we demonstrated that in mice with advanced tumors (where MDSC-induced suppression was present), treatment with a single low-dose Flu (25, 50, 100mg/kg) elevated the numbers of splenic MDSCs and serum arginase activity, and simultaneously, increased the tumor growth (only the highest dose)...
April 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28398610/flavonoids-of-rosa-roxburghii-tratt-exhibit-anti-apoptosis-properties-by-regulating-parp-1-aif
#2
REVIEW
Ping Xu, Xingxia Liu, Xiwen Xiong, Wenbo Zhang, Xinhua Cai, Peiyong Qiu, Minghua Hao, Lijuan Wang, Dandan Lu, Xiuhua Zhang, Wancai Yang
Radioprotection is an important approach to reduce the side-effects of radiotherapy. The radioprotective effect of the flavonoids of Rosa roxburghii Tratt (FRT) has been confirmed, and the mechanism has been identified as theBcl-2/caspase-3/PARP-1 signaling pathway. In this study, we investigated the effects of FRT on the intercellular adhesion molecule (ICAM), and vascular cell adhesion protein (VCAM) in addition to apoptosis-related proteins such as Bax/Bcl-2, p-ERK/ERK, p-p53/p53, and p-p38/p38. In the present study, we focused on the effect of FRT on PARP-1/AIF...
April 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28397794/protein-malnutrition-promotes-dysregulation-of-molecules-involved-in-t-cell-migration-in-the-thymus-of-mice-infected-with-leishmania-infantum
#3
Monica Losada-Barragán, Adriana Umaña-Pérez, Sergio Cuervo-Escobar, Luiz Ricardo Berbert, Renato Porrozzi, Fernanda N Morgado, Daniella Areas Mendes-da-Cruz, Wilson Savino, Myriam Sánchez-Gómez, Patricia Cuervo
Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397358/depletion-resistant-cd4-t-cells-enhance-thymopoiesis-during-lymphopenia
#4
Katayoun Ayasoufi, Ran Fan, Anna Valujskikh
Lymphoablation is routinely used in transplantation, and its success is defined by the balance of pathogenic versus protective T cells within reconstituted repertoire. While homeostatic proliferation and thymopoiesis may both cause T cell recovery during lymphopenia, the relative contributions of these mechanisms remain unclear. The goal of this study was to investigate the role of the thymus during T cell reconstitution in adult allograft recipients subjected to lymphoablative induction therapy. Compared to euthymic mice, thymectomized heart allograft recipients demonstrated severely impaired CD4 and CD8 T cell recovery and prolonged heart allograft survival after lymphoablation with murine anti-thymocyte globulin (mATG)...
April 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28390983/allogeneic-stem-cell-transplantation-for-relapsed-refractory-b-cell-lymphomas-results-of-a-multicenter-phase-ii-prospective-trial-including-rituximab-in-the-reduced-intensity-conditioning-regimen
#5
Anna Dodero, Francesca Patriarca, Giuseppe Milone, Barbara Sarina, Rosalba Miceli, Anna Iori, Francesco Barretta, Elisabetta Terruzzi, Alberto Mussetti, Massimo Pini, Alberto Bosi, Alida Dominietto, Nicola Cascavilla, Francesco Onida, Franco Narni, Lucia Farina, Alessandro Rambaldi, Paolo Corradini
The treatment of patients with refractory/relapsed B-Cell non-Hodgkin lymphoma (NHL) is evolving due to the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicentre prospective phase II trial to evaluate the benefit of including only one dose of Rituximab (R) in the conditioning regimen before alloSCT. The primary end-point was progression-free survival. The study enrolled 121 patients with relapsed/refractory B-cell lymphomas...
April 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28389319/in-vitro-immunoregulatory-effects-of-thymoglobulin-on-human-immune-cell-subpopulations
#6
Maja Buszko, Bojana Jakic, Christian Ploner, Paul Hoertnagl, Christina Mayerl, Georg Wick, Giuseppe Cappellano
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent in organ transplantation. Its polyclonal character suggests that its effect may go far beyond just T cell depletion. The aim of this study was to further elucidate possible mechanisms underlying the suppressive activity of ATG. For in vitro studies, human peripheral blood mononuclear cells (PBMC) were incubated with ATG or control Ig for various time points. Foxp3(+) regulatory cells (Tregs) and monocytes were phenotypically analyzed by flow cytometry and functionally tested by in vitro suppression assays...
April 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28386277/thyroid-related-protein-expression-in-the-human-thymus
#7
Mi Jeong Kim, So Won Oh, Hyewon Youn, Juri Na, Keon Wook Kang, Do Joon Park, Young Joo Park, Ja June Jang, Kyu Eun Lee, Kyeong Cheon Jung, June-Key Chung
Radioiodine whole body scan (WBS), related to sodium iodide symporter (NIS) function, is widely used to detect recurrence/metastasis in postoperative patients with thyroid cancer. However, the normal thymic uptake of radioiodine has occasionally been observed in young patients. We evaluated the expression of thyroid-related genes and proteins in the human thymus. Thymic tissues were obtained from 22 patients with thyroid cancer patients of all ages. The expression of NIS, thyroid-stimulating hormone receptor (TSHR), thyroperoxidase (TPO), and thyroglobulin (Tg) was investigated using immunohistochemistry and quantitative RT-PCR...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28382035/heritable-gene-regulation-in-the-cd4-cd8-t-cell-lineage-choice
#8
REVIEW
Priya D A Issuree, Charles P Ng, Dan R Littman
The adaptive immune system is dependent on functionally distinct lineages of T cell antigen receptor αβ-expressing T cells that differentiate from a common progenitor in the thymus. CD4(+)CD8(+) progenitor thymocytes undergo selection following interaction with MHC class I and class II molecules bearing peptide self-antigens, giving rise to CD8(+) cytotoxic and CD4(+) helper or regulatory T cell lineages, respectively. The strict correspondence of CD4 and CD8 expression with distinct cellular phenotypes has made their genes useful surrogates for investigating molecular mechanisms of lineage commitment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28381565/tetherin-inhibits-cell-free-virus-dissemination-and-retards-murine-leukemia-virus-pathogenesis
#9
Rachel A Liberatore, Emily J Mastrocola, Chelsea Powell, Paul D Bieniasz
The relative contributions of cell-free virion circulation versus direct cell-to-cell transmission to retroviral dissemination and pathogenesis are unknown. Tetherin/Bst2 is an antiviral protein that blocks enveloped virion release into the extracellular milieu, but may not inhibit cell-to-cell virus transmission. We developed live-cell imaging assays which show that tetherin does not affect Moloney murine leukemia virus (MoMLV) spread, and only minimally affects vesicular stomatitis virus (VSV) spread, to adjacent cells in a monolayer...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28377772/treatment-of-pediatric-acute-graft-versus-host-disease-lessons-from-primary-immunodeficiency
#10
REVIEW
Aisling M Flinn, Andrew R Gennery
Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28376432/expression-and-splicing-of-ikaros-family-members-in-murine-and-human-thymocytes
#11
Julie L Mitchell, Amara Seng, Thomas M Yankee
The Ikaros family of transcription factors includes five highly homologous members that can homodimerize or heterodimerize in any combination. Dimerization is essential for their ability to bind DNA and function as transcription factors. Previous studies showed that eliminating the function of the entire family blocks lymphocyte development while deletion of individual family members has relatively minor defects. These data indicate that multiple family members function during T cell development, so we examined the changes in expression of each family member as thymocytes progressed from the CD4(-)CD8(-) double negative (DN) to the CD4(+)CD8(+) double positive (DP) developmental stage...
April 1, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28373584/invariant-nkt-cell-activation-is-potentiated-by-homotypic-trans-ly108-interactions
#12
Yuriy Baglaenko, Mayra Cruz Tleugabulova, Eric Gracey, Nafiseh Talaei, Kieran Patricia Manion, Nan-Hua Chang, Dario Michael Ferri, Thierry Mallevaey, Joan E Wither
Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored...
April 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28373413/acute-graft-versus-host-disease-a-comprehensive-review
#13
REVIEW
Samah Nassereddine, Hind Rafei, Ehab Elbahesh, Imad Tabbara
Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28369956/anti-thymocyte-serum-as-part-of-an-immunosuppressive-regimen-in-treating-haematological-immune-mediated-diseases-in-dogs
#14
B Cuq, S L Blois, K A Mathews
OBJECTIVES: To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. METHODS: Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded...
March 28, 2017: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/28362433/il-2-prevents-deletion-of-developing-t-regulatory-cells-in-the-thymus
#15
Daniel Y Hu, Rushika C Wirasinha, Christopher C Goodnow, Stephen R Daley
In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28361127/longterm-maintenance-of-human-naive-t-cells-through-in-situ-homeostasis-in-lymphoid-tissue-sites
#16
Joseph J C Thome, Boris Grinshpun, Brahma V Kumar, Masa Kubota, Yoshiaki Ohmura, Harvey Lerner, Gregory D Sempowski, Yufeng Shen, Donna L Farber
Naïve T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human lifespan remain undefined. Here, we investigated human naïve T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 3 months-73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors over age 40 coincident with reduced recent thymic emigrants (RTE) in lymphoid tissues, while naïve T cells were functionally maintained predominantly in lymph nodes (LN)...
December 2016: Science Immunology
https://www.readbyqxmd.com/read/28355720/-the-clinical-characteristics-of-adult-hemophagocytic-lymphohistiocytosis-treated-with-haploidentical-donor-hematopoietic-stem-cell-transplantation
#17
L Fu, N Wei, J S Wang, L Wu, Y N Wang, D Y Huang, J L Liu, Z Wang
Objective: To analyze the clinical characteristics of adult patients with hemophagocytic lymphohistiocytosis (HLH) receiving haploidentical donor hematopoietic stem cell transplantation (HID HSCT). Method: We retrospectively reviewed 20 adult patients with HLH from August 2009 to August 2014.The clinical features and outcome were analyzed. Results: Conditioning regimens consisted of total body irradiation/etoposide/cyclophosphamide (TBI/VP-16/CTX) and busulfan (Bu)/VP-16/CTX in HLH with anti-thymocyte globulin (ATG) 8 mg/kg...
April 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-non-myeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#18
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28349472/analysis-of-thymocyte-migration-cellular-interactions-and-activation-by-multiphoton-fluorescence-microscopy-of-live-thymic-slices
#19
Jessica N Lancaster, Lauren I R Ehrlich
Thymocytes migrate through discrete compartments within the thymus, engaging in cellular interactions essential for their differentiation into functional and self-tolerant T cells. Thus, understanding the temporal and spatial behavior of thymocytes within an intact thymic microenvironment is critical for elucidating processes governing T cell development. Towards this end, we describe methods for preparing thymic explant slices, in which the migration of thymocytes through three-dimensional space can be probed using time-lapse, multiphoton fluorescence microscopy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349053/immunomodulatory-effects-of-saccharomyces-cerevisiae-fermentation-product-supplementation-on-immune-gene-expression-and-lymphocyte-distribution-in-immune-organs-in-broilers
#20
Wen K Chou, Jungwoo Park, John B Carey, Don R McIntyre, Luc R Berghman
A study was conducted to evaluate the molecular and cellular immunomodulatory effects of a Saccharomyces cerevisiae fermentation product (Original XPC, Diamond V) in broilers. Our lab has previously demonstrated that broilers fed XPC generate faster and stronger antigen-specific humoral immune responses to Newcastle disease virus (NDV) vaccination. This study aims at investigating the mechanism behind this increased immunocompetence. One-day-old broilers were randomly assigned to one of two treatments: 1.25 kg/ton S...
2017: Frontiers in Veterinary Science
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