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https://www.readbyqxmd.com/read/28077598/notch-ligand-delta-like-4-promotes-regulatory-t-cell-identity-in-pulmonary-viral-infection
#1
Hung-An Ting, Matthew A Schaller, Denise E de Almeida Nagata, Andrew J Rasky, Ivan P Maillard, Nicholas W Lukacs
Regulatory T (Treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on APC after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in Treg cell differentiation, stability, and function in RSV infection. We found that Dll4 was expressed on CD11b(+) pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after RSV infection...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#2
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#3
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28039309/tissue-nonspecific-alkaline-phosphatase-expression-is-needed-for-the-full-stimulation-of-t-cells-and-t-cell-dependent-colitis
#4
Cristina Hernández-Chirlaque, Reyes Gámez-Belmonte, Borja Ocón, Patricia Martínez-Moya, Stefan Wirtz, Fermín Sánchez de Medina, Olga Martínez-Augustin
BACKGROUND AND AIMS: Two alkaline phosphatase isoforms, intestinal (IAP) and tissue non-specific alkaline phosphatase (TNAP), are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes using heterozygous TNAP(+/-) mice (as TNAP(-/-) mice are nonviable). METHODS: In vitro primary cultures and in vivo T cell models using TNAP(+/-) mice were used. RESULTS: Stimulated splenocytes (lipopolysaccharide and concanavalin A) and T lymphocytes (concanavalin A and a-CD3/a-CD28) showed a decreased cytokine production and expression when compared with WT cells...
December 30, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/27989714/ifny-and-ifny-treg-subsets-with-stable-and-unstable-foxp3-expression-in-kidney-transplant-recipients-with-good-long-term-graft-function
#5
Karina Trojan, Christian Unterrainer, Mostafa Aly, Li Zhu, Rolf Weimer, Nuray Bulut, Christian Morath, Gerhard Opelz, Volker Daniel
BACKGROUND: Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function. METHOD: Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry. Foxp3 TSDR methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations using high resolution melt analysis...
October 29, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27906487/neutrophil-activation-during-acute-human-anaphylaxis-analysis-of-mpo-and-scd62l
#6
Abbie Francis, Erika Bosio, Shelley F Stone, Daniel M Fatovich, Glenn Arendts, Yusuf Nagree, Stephen P J Macdonald, Hugh Mitenko, Mani Rajee, Sally Burrows, Simon G A Brown
BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the Emergency Department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time points...
December 1, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27905913/sera-from-severe-trauma-patients-with-pneumonia-and-without-infectious-complications-have-differential-effects-on-neutrophil-biology
#7
B Relja, R Taraki, M P J Teuben, K Mörs, N Wagner, S Wutzler, F Hildebrand, M Perl, I Marzi
BACKGROUND: Major trauma patients (TP) developing imbalanced immune response are at high risk for infectious post-injury complications including pneumonia. Neutrophils play a central role in the host defense against bacteria and thereby pathogenesis of infections. While there are numerous studies about neutrophil function after trauma, data about their biology in patients who suffer from pneumonia following trauma are sparse. Here, we studied the effect of serum isolated from patients who do and do not develop infection (inf...
December 1, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#8
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27884732/natural-killer-cell-subsets-and-receptor-expression-in-peripheral-blood-mononuclear-cells-of-a-healthy-korean-population-reference-range-influence-of-age-and-sex-and-correlation-between-nk-cell-receptors-and-cytotoxicity
#9
Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, Duck Cho
BACKGROUND: The purpose of this study was to identify CD56(bright) and CD56(dim) natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3(-)/CD56(dim) and CD3(-)/CD56(bright) NK cells in whole-blood samples from 122 healthy donors...
November 21, 2016: Human Immunology
https://www.readbyqxmd.com/read/27877175/thymocytes-in-lyve1-cre-s1pr1-f-f-mice-accumulate-in-the-thymus-due-to-cell-intrinsic-loss-of-sphingosine-1-phosphate-receptor-expression
#10
Akira Takeda, Mohammad Shahadat Hossain, Pia Rantakari, Szandor Simmons, Naoko Sasaki, Marko Salmi, Sirpa Jalkanen, Masayuki Miyasaka
T cell emigration from the thymus is essential for immunological homeostasis. While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to promote thymocyte egress via the S1P receptor, S1PR1, the significance of S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains unclear. To address this issue, we developed conditional knockout mice (Lyve1-CRE/S1pr1(f/f) mice) in which S1pr1 was selectively targeted in cells expressing the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were significantly reduced in secondary lymphoid tissues, and CD62L(+) mature CD4 and CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo thymus egress...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27847409/effect-of-interleukin-15-on-cd11b-cd54-and-cd62l-expression-on-natural-killer-cell-and-natural-killer-t-like-cells-in-systemic-lupus-erythematosus
#11
Syh-Jae Lin, Ji-Yih Chen, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Jing-Long Huang
Adhesion molecules may play an important role in systemic lupus erythematosus (SLE) pathogenesis. We investigated the effect of interleukin- (IL-) 15 on CD11b, CD54, and CD62L expression on natural killer (NK) cells, T cells, and CD56(+)CD3(+) NKT-like cells from SLE subjects and healthy controls. SLE patients had decreased circulating NK cells and NKT-like cells compared to controls. NK cells from SLE patients showed higher CD11b and CD62L expression compared to controls. IL-15 enhanced CD11b and CD54 but downregulated CD62L expression on NK cells from SLE patients...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27847359/human-asymptomatic-epitopes-identified-from-the-herpes-simplex-virus-tegument-protein-vp13-14-ul47-preferentially-recall-polyfunctional-effector-memory-cd44highcd62llowcd8-tem-cells-and-protect-humanized-hla-a-02-01-transgenic-mice-against-ocular-herpes
#12
Ruchi Srivastava, Arif A Khan, Sumit Garg, Sabrina A Syed, Julie N Furness, Hawa Vahed, Tiffany Pham, Howard T Yu, Anthony B Nesburn, Lbachir BenMohamed
: The herpes simplex virus type 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8(+) T cells play a role in the "natural protection" seen in asymptomatic (ASYMP) individuals (have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 693 amino acids sequence of VP13/14 protein...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27820846/preclinical-immunomodulation-by-the-probiotic-bifidobacterium-breve-m-16v-in-early-life
#13
Maria Del Mar Rigo-Adrover, Àngels Franch, Margarida Castell, Francisco José Pérez-Cano
This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained...
2016: PloS One
https://www.readbyqxmd.com/read/27816639/diminished-effector-and-memory-cd8-circulating-t-lymphocytes-in-patients-with-severe-influenza-caused-by-the-ah1n1-pdm09-virus
#14
Yolanda Gonzalez, Esmeralda Juárez, Claudia Carranza, Eduardo Sada, Sigifredo Pedraza-Sánchez, Martha Torres
The T cell immune response to viral infection includes the expansion of naïve T cells, effector cell differentiation and the induction of long-lived memory cells. We compared the differentiation of CD8(+) T cells in patients with severe or mild pneumonia induced by influenza infection occurring during the 2009 influenza outbreak and compared their T cell subsets with those in blood samples obtained from healthy volunteers before the AH1N1 influenza outbreak in Mexico. Patients with severe influenza exhibited significantly lower numbers of effector memory CD8(+)CD26 (high) CD45RO(+)CCR7(+) phenotype and lower numbers of central memory CD8(+)CD(26)(high) CD62L(+)CCR7(+), CD26 (high) CD62L(+)CD127(+) or CD26 (high) CD45RO(+)CD57 (low) phenotypes than patients with mild influenza or unexposed healthy subjects...
November 2, 2016: Virology
https://www.readbyqxmd.com/read/27815407/cd62l-test-at-2-years-of-natalizumab-predicts-progressive-multifocal-leukoencephalopathy
#15
Béatrice Pignolet, Nicholas Schwab, Tilman Schneider-Hohendorf, Florence Bucciarelli, Damien Biotti, Delphine Averseng-Peaureaux, Olivier Outteryck, Jean-Claude Ongagna, Jérôme de Sèze, Bruno Brochet, Jean-Christophe Ouallet, Marc Debouverie, Sophie Pittion, Gilles Defer, Nathalie Derache, Patrick Hautecoeur, Ayman Tourbah, Pierre Labauge, Giovanni Castelnovo, Pierre Clavelou, Eric Berger, Jean Pelletier, Audrey Rico, Hélène Zéphir, David Laplaud, Sandrine Wiertlewski, William Camu, Eric Thouvenot, Olivier Casez, Thibault Moreau, Agnès Fromont, Sandra Vukusic, Caroline Papeix, Patrick Vermersch, Manuel Comabella, Christine Lebrun-Frenay, Heinz Wiendl, David Brassat
No abstract text is available yet for this article.
December 6, 2016: Neurology
https://www.readbyqxmd.com/read/27812850/generation-of-t-cell-effectors-using-tumor-cell-loaded-dendritic-cells-for-adoptive-t-cell-therapy
#16
Katerina Vavrova, Petra Vrabcova, Dominik Filipp, Jirina Bartunkova, Rudolf Horvath
Adoptive T cell transfer has been shown to be an effective method used to boost tumor-specific immune responses in several types of malignancies. In this study, we set out to optimize the ACT protocol for the experimental treatment of prostate cancer. The protocol includes a pre-stimulation step whereby T cells were primed with autologous dendritic cells loaded with the high hydrostatic pressure-treated prostate cancer cell line, LNCaP. Primed T cells were further expanded in vitro with anti-CD3/CD28 Dynabeads in the WAVE bioreactor 2/10 system and tested for cytotoxicity...
December 2016: Medical Oncology
https://www.readbyqxmd.com/read/27807194/therapeutic-targeting-of-the-g-csf-receptor-reduces-neutrophil-trafficking-and-joint-inflammation-in-antibody-mediated-inflammatory-arthritis
#17
Ian K Campbell, David Leong, Kirsten M Edwards, Veronika Rayzman, Milica Ng, Gabrielle L Goldberg, Nicholas J Wilson, Karen Scalzo-Inguanti, Charley Mackenzie-Kludas, Kate E Lawlor, Ian P Wicks, Lorena E Brown, Adriana Baz Morelli, Con Panousis, Michael J Wilson, Andrew D Nash, Brent S McKenzie, Arna E Andrews
G-CSF is a hemopoietic growth factor that has a role in steady state granulopoiesis, as well as in mature neutrophil activation and function. G-CSF- and G-CSF receptor-deficient mice are profoundly protected in several models of rheumatoid arthritis, and Ab blockade of G-CSF also protects against disease. To further investigate the actions of blocking G-CSF/G-CSF receptor signaling in inflammatory disease, and as a prelude to human studies of the same approach, we developed a neutralizing mAb to the murine G-CSF receptor, which potently antagonizes binding of murine G-CSF and thereby inhibits STAT3 phosphorylation and G-CSF receptor signaling...
November 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27797936/il-6-and-pd-l1-antibody-blockade-combination-therapy-reduces-tumour-progression-in-murine-models-of-pancreatic-cancer
#18
Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
OBJECTIVE: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. DESIGN: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively...
October 21, 2016: Gut
https://www.readbyqxmd.com/read/27781132/immunomodulation-of-inflammatory-leukocyte-markers-during-intravenous-immunoglobulin-treatment-associated-with-clinical-efficacy-in-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#19
Wayne B Dyer, Joanne C G Tan, Timothy Day, Lynette Kiers, Matthew C Kiernan, Con Yiannikas, Stephen Reddel, Karl Ng, Phillip Mondy, Peta M Dennington, Melinda M Dean, Halina M Trist, Cristobal Dos Remedios, P Mark Hogarth, Steve Vucic, David O Irving
OBJECTIVE: The objective of the study was to profile leukocyte markers modulated during intravenous immunoglobulin (IVIg) treatment, and to identify markers and immune pathways associated with clinical efficacy of IVIg for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with potential for monitoring treatment efficacy. METHODS: Response to IVIg treatment in newly diagnosed IVIg-naïve and established IVIg-experienced patients was assessed by changes in expression of inflammatory leukocyte markers by flow cytometry...
October 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27780229/a-comparison-of-human-neutrophils-acquired-from-four-experimental-models-of-inflammation
#20
Alexander A Maini, Marc J George, Madhur P Motwani, Richard M Day, Derek W Gilroy, Alastair J O'Brien
Defects in neutrophil function have been implicated in a wide spectrum of clinical conditions. Several models are employed to study activated human neutrophils akin to those found at a site of inflammation. These include whole blood (WB) ex vivo stimulation with lipopolysaccharide (LPS) and in vivo techniques: cantharidin blister, skin windows and intra-dermal injection of UV-killed E.coli (UVKEc). Neutrophils obtained from these have never been compared. We compared the activation status of neutrophils from each technique in order to inform the optimal model for use in human studies...
2016: PloS One
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