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Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Honggeng Guan, Yuqiu Wan, Jing Lan, Qin Wang, Zhangyu Wang, Yecheng Li, Jiqing Zheng, Xueguang Zhang, Zemin Wang, Yueping Shen, Fang Xie
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19(+) CD24(+) CD38(+) regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4(+) CD25(+) CD127(-) Tregs (r = 0...
October 20, 2016: Scientific Reports
Yu-Ling Chen, Yi-Ting Chen, Cheng-Feng Lo, Ching-I Hsieh, Shang-Yi Chiu, Chang-Yen Wu, Yu-Shan Yeh, Shu-Hsuan Hung, Po-Hao Cheng, Yu-Hsuan Su, Si-Tse Jiang, Hsian-Jean Chin, Yu-Chia Su
Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn's disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25(-)CD45RB(hi)CD4(+) (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has sufficient sensitivity nor totally matches the pathological findings of CD...
October 20, 2016: Scientific Reports
Monika Ryba-Stanisławowska, Paulina Werner, Maria Skrzypkowska, Agnieszka Brandt, Jolanta Myśliwska
IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4(+)CD25(high)FOXP3(+) T cells...
2016: Mediators of Inflammation
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Rikki A Cannioto, Lara E Sucheston-Campbell, Shalaka Hampras, Ellen L Goode, Keith Knutson, Roberta Ness, Francesmary Modugno, Paul K Wallace, J Brian Szender, Paul Mayor, Chi-Chen Hong, Janine M Joseph, Grace Friel, Warren Davis, Mary Nesline, Kevin H Eng, Robert P Edwards, Bridget Kruszka, Kristina Schmitt, Kunle Odunsi, Kirsten B Moysich
OBJECTIVE: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer...
October 18, 2016: International Journal of Gynecological Cancer
Qingsheng Li, Nejat K Egilmez
The critical contribution of CD4+CD25+Foxp3+ T-regulatory cells (Treg) to immune suppression in the tumor microenvironment is well-established. Whereas the mechanisms that drive the generation and accumulation of Treg in tumors have been an active area of study, the information on their origin and population dynamics remains limited. In this review, we discuss the ontogeny of tumor-associated Treg in light of the recently identified lineage markers.
October 19, 2016: Immunological Investigations
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Katarzyna Sznurkowska, Anton Żawrocki, Jacek Sznurkowski, Maciej Zieliński, Piotr Landowski, Katarzyna Plata-Nazar, Ewa Iżycka-Świeszewska, Piotr Trzonkowski, Agnieszka Szlagatys-Sidorkiewicz, Barbara Kamińska
BACKGROUND/AIMS: To determine the proportion of T-regulatory cells (CD4(+)CD25(high)FOXP3(+) cells) in peripheral blood and the number of FOXP3(+) cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease. MATERIAL AND METHODS: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively...
October 19, 2016: Immunological Investigations
Arash Pourgholaminejad, Nasser Aghdami, Hossein Baharvand, Seyed Mohammad Moazzeni
T-Helper 17 (TH17) cells are a CD4(+) TH subset that plays a critical role in the pathophysiology of inflammatory disorders, especially chronic forms. It seems that the derivation of TH17 cells from their precursors take place in inflammatory microenvironment. The role of transforming growth factor (TGF)-β as an anti-inflammatory cytokine in TH17 cell differentiation is controversial. To address some of the discrepancies that exist among different studies, this study was undertaken to more clarify the TGFβ role in human TH17 cell differentiation...
October 18, 2016: Journal of Immunotoxicology
Xiao-Wen Zhu, Hai-Zhen Zhu, You-Qing Zhu, Mao-Hui Feng, Jian Qi, Zhi-Fen Chen
The mechanism underlying CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4(+)CD25(+)Foxp3(+)Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Xuanyi Meng, Xin Li, Jinyan Gao, Hongbing Chen
Bovine α-lactalbumin (ALA) is a known food allergen present in milk to induce anaphylaxis. A previous study demonstrated that irradiated ALA (iALA) decreased the IgE-binding properties and weakened the degranulation capacity of basophils in vitro. The present study aimed to further assess the potential allergenicity of iALA in vivo in a BALB/c mouse model. The mice (n = 10/group) were intragastrically sensitized and orally challenged with either iALA or ALA using cholera toxin as adjuvant. In contrast to the ALA group, the iALA group did not show anaphylactic shock symptoms...
October 13, 2016: Food and Chemical Toxicology
Catherine Daniel, Marie Titecat, Sabine Poiret, Delphine Cayet, Denise Boutillier, Michel Simonet, Jean-Claude Sirard, Nadine Lemaître, Florent Sebbane
BACKGROUND: Pseudotuberculosis is an infection caused by the bacterial enteropathogen Yersinia pseudotuberculosis and is considered to be a significant problem in veterinary medicine. We previously found that intranasal administration of a recombinant Lactococcus lactis strain that secretes the low-calcium response V (LcrV) antigen from Y. pseudotuberculosis (Ll-LcrV) confers protection against a lethal Y. pseudotuberculosis infection. Here, we aimed at characterizing the immunological basis of this LcrV-elicited protective response and at determining the duration of vaccine-induced immunity...
October 11, 2016: Vaccine
Lanshan Huang, Sa A Wang, Sergej Konoplev, Carlos E Bueso-Ramos, Beenu Thakral, Roberto N Miranda, Elias Jabbour, L Jeffrey Medeiros, Rashmi Kanagal-Shamanna
INTRODUCTION: Well-differentiated systemic mastocytosis (WDSM) is a rare, recently recognized provisional subvariant of systemic mastocytosis (SM). We report a case of WDSM that showed excellent clinical and cutaneous response to imatinib in the absence of known molecular genetic abnormalities. CLINICAL FINDINGS/DIAGNOSES: We present a 24-year-old woman with childhood onset of skin manifestations that progressed to mediator-related systemic events, and a gastrointestinal tract mastocytoma...
October 2016: Medicine (Baltimore)
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Kazunori Nakase, Kenkichi Kita, Taiichi Kyo, Naoyuki Katayama
No abstract text is available yet for this article.
October 13, 2016: Leukemia & Lymphoma
Christina Kalpadakis, Gerassimos A Pangalis, Theodoros P Vassilakopoulos, Maria Roumelioti, Sotirios Sachanas, Penelope Korkolopoulou, Efstathios Koulieris, Maria Moschogiannis, Xanthi Yiakoumis, Pantelis Tsirkinidis, Charalampos Pontikoglou, Dimitra Rondoyianni, Helen A Papadaki, Panayiotidis Panayiotidis, Maria K Angelopoulou
Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM...
October 13, 2016: Hematological Oncology
Christian Pagnoux
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated...
September 2016: Eur J Rheumatol
Mirjam A Lips, Jan Bert van Klinken, Hanno Pijl, Ignace Janssen, Ko Willems van Dijk, Frits Koning, Vanessa van Harmelen
INTRODUCTION: Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking. METHODS: Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP...
November 2016: Metabolism: Clinical and Experimental
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