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cd3 double negative

Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
A Kaszuba, A Konior, T Mikolajczyk, A Prejbisz, M Kabat, I Cendrowska-Demkow, P Dobrowolski, B Pregowska-Chwala, K Michel-Rowicka, A Klisiewicz, P Michalek, S Toutounchi, Z Galazka, M Reincke, A Januszewicz, Tj Guzik
OBJECTIVE: Role of the T cells in pathogenesis of hypertension has been demonstrated in numerous mouse models, limited data is available in human hypertension. Therefore the aim of our study was to quantify blood T lymphocyte subsets, characterized by expression of CD25 markers (CD3 + , CD8 + and CD3 + CD4-CD8- cells) and expression of perforin and granzyme (in CD8 + cells) in subjects with primary hyperaldosteronism (PA), resistant hypertension (RHT) characterized by increased cardiovascular risk and excessive amounts of circulating aldosterone in comparison to controls matched for age, sex and BMI(control group, CG)...
September 2016: Journal of Hypertension
Holger Bronger, Judith Singer, Claudia Windmüller, Ute Reuning, Daniela Zech, Claire Delbridge, Julia Dorn, Marion Kiechle, Barbara Schmalfeldt, Manfred Schmitt, Stefanie Avril
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown. METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10...
August 23, 2016: British Journal of Cancer
Hideki Ishibashi, Satoshi Nimura, Yoshiyuki Kayashima, Yasushi Takamatsu, Kunihiko Aoyagi, Naohiko Harada, Masanori Kadowaki, Takihiko Kamio, Shotaro Sakisaka, Morishige Takeshita
BACKGROUND: In East Asia, monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as type II enteropathy-associated T-cell lymphoma (EATL), occurs more frequently than type I EATL, and coeliac disease is rare. CASE PRESENTATION: Here we present four cases of MEITL in Japanese patients, including the endoscopic and pathological findings of their duodenal and colorectal lesions. Tumor specimens obtained from duodenal, intestinal, and colorectal biopsies in all four patients showed a diffuse intramucosal infiltration of small to/or medium-sized lymphoma cells and numerous atypical intraepithelial lymphocytes (IELs)...
2016: Diagnostic Pathology
Maja M Janas, Yongfeng Jiang, Richard G Duncan, Antoinette N Hayes, Ju Liu, Pia V Kasperkovitz, Michael E Placke, Scott A Barros
Registration of pharmaceuticals requires an assessment of their genotoxic potential using in vitro and in vivo tests outlined in the International Conference on Harmonisation (ICH) guidance S2(R1). We have evaluated numerous siRNA-N-acetylgalactosamine (GalNAc) conjugates containing phosphorothioate linkages and various combinations of 2'-fluoro and 2'-O-methyl ribose modifications of multiple nucleotides in the ICH battery of assays, all of which have uniformly yielded negative results. To verify these negative genotoxicity results, in this study we confirm test article exposure using toolkit small interfering RNAs (siRNAs) representative of those in the clinic...
July 7, 2016: Nucleic Acid Therapeutics
Nadja Zaborsky, Franz Josef Gassner, Daniela Asslaber, Petra Reinthaler, Ursula Denk, Sabine Flenady, Josefina Piñón Hofbauer, Barbara Danner, Stefan Rebhandl, Andrea Harrer, Roland Geisberger, Richard Greil, Alexander Egle
Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted.By using TCL1 mice as a CLL model, we show that TCR-Vβ7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice...
July 1, 2016: Oncotarget
Roman Rombo, Hans Weiher, Ingo G H Schmidt-Wolf
We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood...
2016: German Medical Science: GMS E-journal
Noé Rodríguez-Rodríguez, Sokratis A Apostolidis, Lauren Fitzgerald, Bronwyn S Meehan, Alexandra J Corbett, José Manuel Martín-Villa, James McCluskey, George C Tsokos, José C Crispín
TCR-αβ(+) double negative (DN) T cells (CD3(+) TCR-αβ(+) CD4(-) CD8(-) NK1.1(-) CD49b(-) ) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro-inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self-reactive CD8(+) T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T-cell population...
June 2016: European Journal of Immunology
Andrew R DiNardo, Anna M Mandalakas, Gugu Maphalala, Godwin Mtetwa, Temhlanga Mndzebele, Piluca Ustero, Makhosazana Hlatshwayo, Emily M Mace, Jordan S Orange, George Makedonas
INTRODUCTION: Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-γ) in response to Mycobacterium tuberculosis (Mtb) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient's TB risk...
2016: Mediators of Inflammation
Anna Carrasco, Fernando Fernández-Bañares, Elisabet Pedrosa, Antonio Salas, Carme Loras, Mercè Rosinach, Montserrat Aceituno, Xavier Andújar, Montserrat Forné, Yamile Zabana, Maria Esteve
BACKGROUND AND AIMS: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. METHODS: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4(+)CD25(+)FOXP3(+)], double positive [DP, CD3(+)CD4(+)CD8(+)] and double negative T cells [DN, CD3(+)CD4(-)CD8(-)], immunohistochemistry [FOXP3, caspase-3], and real-time polymerase chain reaction [PCR] [IFN-γ, IL-17-A, and FOXP3] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases...
September 2016: Journal of Crohn's & Colitis
Anna Carrasco, Maria Esteve, Antonio Salas, Elisabet Pedrosa, Mercè Rosinach, Montserrat Aceituno, Yamile Zabana, Fernando Fernández-Bañares
BACKGROUND: Lymphocytic (LC) and collagenous (CC) colitis are the two major forms of microscopic colitis (MC). The aim of this study was to identify similarities and differences in their mucosal immune characteristics. METHODS: Colonic biopsies from 15 CC, 8 LC, and 10 healthy controls were collected. Mucosal lymphocytes were assessed by flow cytometry. Tissue gene expression and protein levels were determined by real-time PCR and ELISA, respectively. RESULTS: LC patients had lower numbers of CD4(+) and double-positive CD4(+)CD8(+)mucosal T lymphocytes, and higher numbers of CD8(+) and CD4(+)TCRγδ(+) mucosal T cells, compared with controls and CC patients...
September 2016: Journal of Crohn's & Colitis
Huan Xu, Fredine T Lauer, Ke Jian Liu, Laurie G Hudson, Scott W Burchiel
Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As(+3) and MMA(+3) toxicity in mouse thymus cells. Because we know that MMA(+3) inhibits IL-7 signaling in mouse bone marrow pre-B cells, we studied the influence of As(+3) and MMA(+3) on T cell development in the thymus at the earliest stage of T cell development (CD4-CD8-, double negative, DN) which requires IL-7 dependent signaling...
April 15, 2016: Toxicology Letters
Maria-Elisabeth Goebeler, Stefan Knop, Andreas Viardot, Peter Kufer, Max S Topp, Hermann Einsele, Richard Noppeney, Georg Hess, Stefan Kallert, Andreas Mackensen, Kathrin Rupertus, Lothar Kanz, Martin Libicher, Dirk Nagorsen, Gerhard Zugmaier, Matthias Klinger, Andreas Wolf, Brigitte Dorsch, Beate D Quednau, Margit Schmidt, Jürgen Scheele, Patrick A Baeuerle, Eugen Leo, Ralf C Bargou
PURPOSE: Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome-negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL...
April 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Tomasz P Mikolajczyk, Ryszard Nosalski, Piotr Szczepaniak, Klaudia Budzyn, Grzegorz Osmenda, Dominik Skiba, Agnieszka Sagan, Jing Wu, Antony Vinh, Paul J Marvar, Bartlomiej Guzik, Jakub Podolec, Grant Drummond, Heinrich E Lob, David G Harrison, Tomasz J Guzik
Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15...
May 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Akitoyo Hotta, Osamu Fujita, Akihiko Uda, Yoshie Yamamoto, Neekun Sharma, Kiyoshi Tanabayashi, Akio Yamada, Shigeru Morikawa
Francisella tularensis, which causes tularemia, is widely distributed in the Northern hemisphere. F. tularensis strains isolated in Japan are genetically unique from non-Japanese strains; however, their phenotypic properties have not been well studied. Thus, mice were infected with representative Japanese strains of F. tularensis and their virulence and mouse immune responses to them assessed. Of four representative Japanese strains, the Ebina, Jap and Tsuchiya strains were susceptible to H2 O2 and did not grow well intracellularly...
March 2016: Microbiology and Immunology
Qingda Meng, Zhenjiang Liu, Elena Rangelova, Thomas Poiret, Aditya Ambati, Lalit Rane, Shanshan Xie, Caroline Verbeke, Ernest Dodoo, Marco Del Chiaro, Matthias Löhr, Ralf Segersvärd, Markus J Maeurer
Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor-infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry...
February 2016: Journal of Immunotherapy
A Alunno, F Carubbi, O Bistoni, S Caterbi, E Bartoloni, P Di Benedetto, P Cipriani, R Giacomelli, R Gerli
Compelling evidence suggests that interleukin (IL)-17 and IL-17-producing cells play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS). We investigated phenotypical and functional effects of the anti-CD20 antibody rituximab (RTX) on circulating and glandular IL-17-producing T cells in pSS. RTX is able to deplete glandular IL-17(+) CD3(+) CD4(-) CD8(-) double-negative (DN) and CD4(+) Th17 cells as well as circulating IL-17(+) DN T cells. A fraction of glandular and circulating IL-17(+) DN cells and CD4(+) T helper type 17 (Th17) cells co-expresses CD20 on the cell surface explaining, at least in part, such depletive capacity of RTX...
June 2016: Clinical and Experimental Immunology
Jia-peng Sun, Xin-tian Lu, Wei-hong Zhao, Ying Hua
We described 1 case of autoimmune lymphoproliferative syndrome (ALPS), first diagnosed in our hospital, and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection, parvovirus B19 infection and chronic diarrhea disease. Besides, his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha/beta double-negative T cells (DNTs) (27...
December 18, 2015: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Julie L Mitchell, Amara Seng, Thomas M Yankee
In human T cell development, the mechanisms that regulate cell fate decisions after TCRβ expression remain unclear. We defined the stages of T cell development that flank TCRβ expression and found distinct patterns of human T cell development. In half the subjects, T cell development progressed from the CD4(-)CD8(-) double-negative stage to the CD4(+)CD8(+) double-positive (DP) stage through an immature single-positive (ISP) CD4(+) intermediate. However, in some patients, CD4 and CD8 were expressed simultaneously and the ISP population was small...
April 2016: Immunologic Research
Ming-Qi Zhao, Li-Hua Wang, Guang-Wan Lian, Jia-Hui Xie, Min Guo, Ying-Ying Zhang, Bing Zhu
BACKGROUND: Influenza A virus can cause severe respiratory infection in children and even result in immune system dysfunction. The aim of this study is to examine the clinical value of peripheral blood lymphocytes and serum nitric oxide (NO) and cytokines in children with influenza A viral pneumonia. METHODS: Thirty children hospitalized with confirmed influenza A viral pneumonia and 30 healthy controls were enrolled in this study. The blood samples were collected from all the children and anti-coagulated with EDTA...
2015: Clinical Laboratory
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