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https://www.readbyqxmd.com/read/28346024/increased-il-4-and-il-17-producing-cd8-cells-are-related-to-decreased-cd39-cd4-foxp3-cells-in-allergic-asthma
#1
Li Ping, Zhen Yang, Qin Zhang, Wei Wang, Jiong Yang
OBJECTIVE: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen primed CD8(+) T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8(+) T cells and CD39(+) Tregs. METHODS: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i...
March 27, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28345428/induction-of-t-cell-infiltration-and-programmed-death-ligand-2-expression-by-adeno-associated-virus-in-rhesus-macaque-skeletal-muscle-and-modulation-by-prednisone
#2
Megan L Cramer, Guohong Shao, Louise R Rodino-Klapac, Louis G Chicoine, Paul T Martin
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post-AAV delivery compared to AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment...
March 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#3
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344873/a-specific-immune-and-lymphatic-profile-characterizes-the-pre-metastatic-state-of-the-sentinel-lymph-node-in-patients-with-early-cervical-cancer
#4
Cédric Balsat, Silvia Blacher, Michael Herfs, Maureen Van de Velde, Nicolas Signolle, Philippe Sauthier, Charles Pottier, Stéphanie Gofflot, Marjolein De Cuypere, Philippe Delvenne, Frédéric Goffin, Agnès Noel, Frédéric Kridelka
The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#5
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344860/il-32-induces-indoleamine-2-3-dioxygenase-cd1c-dendritic-cells-and-indoleamine-2-3-dioxygenase-cd163-macrophages-relevance-to-mycosis-fungoides-progression
#6
Hanako Ohmatsu, Daniel Humme, Juana Gonzalez, Nicholas Gulati, Markus Möbs, Wolfram Sterry, James G Krueger
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c(+) myeloid dendritic cells (mDC) and/or CD163(+) macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344516/ulinastatin-ameliorates-tissue-damage-of-severe-acute-pancreatitis-through-modulating-regulatory-t-cells
#7
Yu Pan, Haizong Fang, Fengchun Lu, Minggui Pan, Fei Chen, Ping Xiong, Yi Yao, Heguang Huang
BACKGROUND: Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP. METHODS: We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28343267/tumor-associated-macrophages-and-regulatory-t-cells-infiltration-and-the-clinical-outcome-in-colorectal-cancer
#8
Dariusz Waniczek, Zbigniew Lorenc, Mirosław Śnietura, Mariusz Wesecki, Agnieszka Kopec, Małgorzata Muc-Wierzgoń
The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68(+)/iNOS(-) and Tregs CD8(+)/FoxP3(+) in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases)...
March 25, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#9
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28337956/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#10
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols...
March 23, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28337881/indoleamine-2-3-dioxygenase-and-regulatory-t-cells-in-intestinal-mucosa-in-children-with-inflammatory-bowel-disease
#11
K Sznurkowska, A Żawrocki, J Sznurkowski, E Iżycka-Świeszewska, P Landowski, A Szlagatys-Sidorkiewicz, K Plata-Nazar, B Kamińska
Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28333137/the-mtor-signal-regulates-myeloid-derived-suppressor-cells-differentiation-and-immunosuppressive-function-in-acute-kidney-injury
#12
Chao Zhang, Shuo Wang, Jiawei Li, Weitao Zhang, Long Zheng, Cheng Yang, Tongyu Zhu, Ruiming Rong
The mammalian target of rapamycin (mTOR) signal controls innate and adaptive immune response in multiple immunoregulatory contexts. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells of potent immunosuppressive capacity. In this study, we aimed to investigate the role of MDSCs in the protection of acute kidney injury (AKI) and the regulation of mTOR signal on MDSC's protective role in this context. In mice AKI model, rapamycin administration was associated with improved renal function, restored histological damage and decreased CD4(+) and CD8(+) T-cell infiltration in kidney tissue...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332605/janus-faced-acrolein-prevents-allergy-but-accelerates-tumor-growth-by-promoting-immunoregulatory-foxp3-cells-mouse-model-for-passive-respiratory-exposure
#13
Franziska Roth-Walter, Cornelia Bergmayr, Sarah Meitz, Stefan Buchleitner, Caroline Stremnitzer, Judit Fazekas, Anna Moskovskich, Mario A Müller, Georg A Roth, Krisztina Manzano-Szalai, Zdenek Dvorak, Alina Neunkirchner, Erika Jensen-Jarolim
Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#14
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#15
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28324830/chitinase-3-like-1-deficient-donor-splenocytes-accentuated-the-pathogenesis-of-acute-graft-versus-host-diseases-through-regulating-t-cell-expansion-and-type-i-inflammation
#16
Zengyao Li, Jian Gu, Jing Liu, Qin Zhu, Hao Lu, Yunjie Lu, Jianhua Rao, Ling Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is a major complication following transplantation, limiting the success of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family, plays a critical role in bacterial infections, allergic disease and a variety of malignancies. Here, we investigated whether CHI3L1 could affect the pathogenesis of aGVHD in a mouse allo-HCT model. In this study, we show that CHI3L1 deficiency in donor T cells increased the severity of aGVHD through enhancing systemic and local inflammation...
March 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28324192/the-presence-of-human-papillomavirus-hpv-in-placenta-and-or-cord-blood-might-result-in-th2-polarization
#17
H-M Koskimaa, A Paaso, M J P Welters, S Grénman, K Syrjänen, S H van der Burg, S Syrjänen
The purpose of this study was to evaluate if an early exposure to human papillomavirus (HPV) during the prenatal period or infancy could result in HPV16-specific T helper (Th) responses resembling those of adults with HPV-induced lesions. We tested HPV16-specific cell-mediated immunity (CMI) in children born with HPV-positive umbilical cord blood and/or placenta or having persistent oral HPV infection and in constantly oral HPV-negative controls. Peripheral blood mononuclear cells from 33 children from the Finnish HPV Family Study cohort (mean age 14...
March 21, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28322245/tumour-infiltrating-lymphocytes-correlate-with-improved-survival-in-patients-with-esophageal-squamous-cell-carcinoma
#18
Dongxian Jiang, Yalan Liu, Hao Wang, Haixing Wang, Qi Song, Akesu Sujie, Jie Huang, Yifan Xu, Haiying Zeng, Lijie Tan, Yingyong Hou, Chen Xu
We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin-stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321419/pvaxhsp65-vaccination-primes-for-high-il-10-production-and-decreases-experimental-encephalomyelitis-severity
#19
Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, Thais Graziela Donegá França, Larissa Lumi Watanabe Ishikawa, Larissa Camargo da Rosa, Priscila Maria Colavite, Bianca Balbino, Camila Marques, Maura Rosane Valerio Ikoma, Ana Paula Masson, Célio Lopes Silva, Alexandrina Sartori
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#20
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
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