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José V Subiela, Sonia H Torres, Juan B De Sanctis, Noelina Hernández
There is evidence that myocardial infarction (MI) patients have an inflammatory process that includes skeletal muscles, and exercise has been reported to reduce some inflammatory markers. The aim of this work was to study NO and some inflammatory markers in quadriceps muscle of MI patients before and after cardiac rehabilitation. Muscle biopsy was obtained in17 MI patients before and after CR and only once in 11 healthy subjects. Several cardiorespiratory and metabolic parameters were evaluated and skeletal muscle levels of nitric oxide synthases, nitrate, nitrite, nitrotyrosine, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin- 6 (IL-6) and CD154...
March 10, 2018: Nitric Oxide: Biology and Chemistry
M Cecilia Berin, Alexander Grishin, Madhan Masilamani, Donald Y Leung, Scott H Sicherer, Stacie M Jones, A Wesley Burks, Alice K Henning, Peter Dawson, Joanna Grabowska, Charuta Agashe, Wendy F Davidson, Robert A Wood, Hugh A Sampson
BACKGROUND: Egg allergy is phenotypically heterogeneous. A subset of egg allergic individuals can tolerate egg in an extensively heated form. Inclusion of baked-egg (BE) into their diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown. OBJECTIVES: To study egg-specific antibody, basophil, and T cell responses in children with reactivity or tolerance to BE...
March 5, 2018: Journal of Allergy and Clinical Immunology
Riccardo Barrile, Andries D van der Meer, Hyoungshin Park, Jacob P Fraser, Damir Simic, Fang Teng, David Conegliano, Justin Nguyen, Abhishek Jain, Mimi Zhou, Katia Karalis, Donald E Ingber, Geraldine A Hamilton, Monicah A Otieno
Clinical development of Hu5c8, a monoclonal antibody against CD40L intended for treatment of autoimmune disorders, was terminated due to unexpected thrombotic complications. These life-threatening side-effects were not discovered during preclinical testing due to the lack of predictive models. In the present study, we describe the development of a microengineered system lined by human endothelium perfused with human whole blood, a 'Vessel-Chip'. The Vessel-Chip allowed us to evaluate key parameters in thrombosis, such as endothelial activation, platelet adhesion, platelet aggregation, fibrin clot formation, and thrombin anti-thrombin (TAT) complexes in the Chip-effluent in response to Hu5c8 in the presence of soluble CD40L...
February 27, 2018: Clinical Pharmacology and Therapeutics
Anna Nowak, Dominik Lock, Petra Bacher, Thordis Hohnstein, Katrin Vogt, Judith Gottfreund, Pascal Giehr, Julia K Polansky, Birgit Sawitzki, Andrew Kaiser, Jörn Walter, Alexander Scheffold
Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cultures is highly variable, and currently, it is impossible to identify and separate stable Tregs from contaminating effector T cells, either ex vivo or after prior expansion...
2018: Frontiers in Immunology
Natalie A O'Neill, Tianshu Zhang, Gheorghe Braileanu, Xiangfei Cheng, Alena Hershfeld, Wenji Sun, Keith A Reimann, Sia Dahi, Natalia Kubicki, Wessam Hassanein, Christopher Laird, Arielle Cimeno, Agnes M Azimzadeh, Richard N Pierson
Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity...
February 2018: Transplantation Direct
Katherine A Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R Neeland, Mimi Lk Tang, Thanh D Dang, Katrina J Allen, Pamela A Frischmeyer-Guerrerio
BACKGROUND: Peanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear. OBJECTIVE: We sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization...
February 14, 2018: Journal of Allergy and Clinical Immunology
Isaac R Melamed, Melinda Heffron, Alessandro Testori, Kellie Lipe
Research has shown that a subset of the autism spectrum disorder (ASD) population presents with immune dysregulation. To explore this topic further, we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. In this study, participants were recruited based on a diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified. Participants also showed evidence of immune dysfunction based on abnormal levels of specific biomarkers, including CD40 ligand (CD154), lymphocyte stimulation, and T or B cell dysfunction...
February 10, 2018: Autism Research: Official Journal of the International Society for Autism Research
David Chiang, Xintong Chen, Stacie M Jones, Robert A Wood, Scott H Sicherer, A Wesley Burks, Donald Y M Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A Sampson, Bojan Losic, M Cecilia Berin
BACKGROUND: The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. OBJECTIVES: Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of individuals with and without peanut allergy (PA). METHODS: We obtained samples from PA individuals, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (CoFAR6)...
January 30, 2018: Journal of Allergy and Clinical Immunology
Eun Wha Choi, Kyo Won Lee, Hyojun Park, Hwajung Kim, Jong Hyun Lee, Ji Woo Song, Jehoon Yang, Yeongbeen Kwon, Tae Min Kim, Jae Berm Park, Sungjoo Kim
Rheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. The CD154-CD40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. Therefore, we aimed to determine whether anti-CD154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. Arthritis was induced using chicken type II collagen (CII) and arthritic monkey were divided into control and anti-CD154 treatment groups based on their concentrations of anti-CII antibodies on week 7 post-immunization...
February 1, 2018: Scientific Reports
Xueyan Zhang, Yanwei Zhang, Jianlin Xu, Huimin Wang, Xiaoxuan Zheng, Yuqing Lou, Baohui Han
The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+ cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of several DC-activating agents...
2018: Journal of Cancer
David A Bernal-Estévez, Oscar García, Ramiro Sánchez, Carlos A Parra-López
BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. METHODS: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C...
January 15, 2018: BMC Cancer
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
Yusmel Sordo, Marisela Suárez, Rosalina Caraballo, Talía Sardina, Emma Brown, Carlos Duarte, Joanna Lugo, Lázaro Gil, Danny Perez, Ayme Oliva, Milagros Vargas, Elaine Santana, Rodolfo Valdés, María Pilar Rodríguez
The development of subunit vaccines against classical swine fever is a desirable goal, because it allows discrimination between vaccinated and infected animals. In this study, humoral and cellular immune response elicited in inbred BALB/c mice by immunization with a recombinant classical swine fever virus (CSFV) E2 protein fused to porcine CD154 antigen (E2CD154) was assessed. This model was used as a predictor of immune response in swine. Mice were immunized with E2CD154 emulsified in Montanide ISA50V2 or dissolved in saline on days 1 and 21...
January 5, 2018: Biologicals: Journal of the International Association of Biological Standardization
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) following an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine ATG (Atgam) and donor bone marrow transplantation (DBMT). Since these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
January 4, 2018: Transplantation
Antonella Cianferoni, Melanie A Ruffner, Ryan Guzek, Shaobo Guan, Terri Brown-Whitehorn, Amanda Muir, Jonathan M Spergel
BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of TH 2 cytokines. OBJECTIVE: To ascertain whether TH 2 cells can exist in the peripheral blood in patients with milk-induced EoE. METHODS: Peripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls...
February 2018: Annals of Allergy, Asthma & Immunology
Tao Li, Yunpeng Shi, Weixia Sun, Haifeng Wang, Quan Wang, Yanfang Jiang
T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1) + Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1 + Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1 + , PD-1 + CD154 + , and PD-1 + interleukin (IL)-21 + Tfh cells, and CD38 + CD19 + and CD38 + CD19 + CD40 + B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0...
February 2018: Molecular Immunology
Avneesh K Singh, Joshua L Chan, Caleb N Seavey, Philip C Corcoran, Robert F Hoyt, Billeta G T Lewis, Marvin L Thomas, David L Ayares, Keith A Horvath, Muhammad M Mohiuddin
BACKGROUND: CD4+CD25Hi FoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long-term baboon recipients who have received genetically modified cardiac xenografts from pig donors...
December 17, 2017: Xenotransplantation
Mariko Ishibashi, Hiromi Yamaguchi, Yukari Hirotani, Akihisa Sakurada, Toshihide Endo, Masahiko Sugitani, Tadatoshi Takayama, Makoto Makishima, Mariko Esumi
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area...
December 16, 2017: Archives of Virology
Tingxi Guo, Ming Yin Koo, Yuki Kagoya, Mark Anczurowski, Chung-Hsi Wang, Kayoko Saso, Marcus O Butler, Naoto Hirano
In humans, a substantial portion of T cells recognize lipids presented by the monomorphic CD1 proteins. Recent studies have revealed the molecular basis of mycobacterial lipid recognition by CD1c-restricted T cells. Subsets of CD1c-restricted T cells recognize self-lipids in addition to foreign lipids, which may have implications in human diseases involving autoimmunity and malignancy. However, the molecular identity of these self-reactive T cells remains largely elusive. In this study, using a novel CD1c+ artificial APC (aAPC)-based system, we isolated human CD1c-restricted autoreactive T cells and characterized them at the molecular level...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Cassandra Balinas, Thao Nguyen, Samantha Johnston, Peter Smith, Donald Staines, Sonya Marshall-Gradisnik
BACKGROUND: Viral infections and hypersensitivities are commonly reported by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. Mast Cells (MC) uniquely mediate type 1 hypersensitivities and resolve viral infections via toll-like receptor 3 (TLR3). OBJECTIVE: To characterise and compare mast cell progenitors (MCPs) in CFS/ME participants with a known MC disorder, Systemic mastocytosis (SM), and secondly, to investigate the role of MC TLR3 in CFS/ME participants following Polyinosinic:polycytidylic acid (Poly I:C) stimulation...
December 10, 2017: Asian Pacific Journal of Allergy and Immunology
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