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Th1 cells

Shenglan Dai, Xiaohua Chen, Yongsheng Yu, Guoqing Zang, Zhenghao Tang
Hepatitis B virus (HBV) infection is a global public health problem. T helper (Th)1‑associated cytokines are involved in HBV clearance during acute and persistent infection. In our previous study, it was demonstrated that lentiviral vectors encoding ubiquitinated hepatitis B core antigen (LV‑Ub‑HBcAg) effectively transduced dendritic cells (DCs) to induce maturation, which promoted T cell polarization to Th1 and generated HBcAg‑specific cytotoxic T lymphocytes (CTLs) ex vivo. In the present study, HBV transgenic mice were immunized with LV‑Ub‑HBcAg‑transduced DCs and HBcAg‑specific immune responses were evaluated...
September 14, 2018: Molecular Medicine Reports
Sophie Langdon, Adina Hughes, Molly A Taylor, Elizabeth A Kuczynski, Deanna A Mele, Oona Delpuech, Laura Jarvis, Anna Staniszewska, Sabina Cosulich, Larissa S Carnevalli, Charles Sinclair
mTOR inhibition can promote or inhibit immune responses in a context dependent manner, but whether this will represent a net benefit or be contraindicated in the context of immunooncology therapies is less understood. Here, we report that the mTORC1/2 dual kinase inhibitor vistusertib (AZD2014) potentiates anti-tumour immunity in combination with anti-CTLA-4 (αCTLA-4), αPD-1 or αPD-L1 immune checkpoint blockade. Combination of vistusertib and immune checkpoint blocking antibodies led to tumour growth inhibition and improved survival of MC-38 or CT-26 pre-clinical syngeneic tumour models, whereas monotherapies were less effective...
2018: Oncoimmunology
Katerina Kachler, Corinna Holzinger, Denis I Trufa, Horia Sirbu, Susetta Finotto
Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+ Foxp3+ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet+ Foxp3+ CD4+ T cells, mediated by the immunosuppressive cytokine TGFβ in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGFβ for the immunopathogenesis of cancer...
2018: Oncoimmunology
Laura E Johnson, Dirk Brockstedt, Meredith Leong, Peter Lauer, Erin Theisen, John-Demian Sauer, Douglas G McNeel
Background . Sipuleucel T, an autologous cell-based vaccine targeting prostatic acid phosphatase (PAP), has demonstrated efficacy for the treatment of advanced prostate cancer. DNA vaccines encoding PAP and live attenuated Listeria vaccines have entered clinical trials for patients with prostate cancer, and have advantages in terms of eliciting predominantly Th1-biased immunity. In this study, we investigated whether the immunogenicity and anti-tumor efficacy of a DNA and Listeria vaccine, each encoding PAP, could be enhanced by using them in a heterologous prime/boost approach...
2018: Oncoimmunology
Kristin Hollister, Praveen Kusumanchi, Ruth Ann Ross, Kristina Chandler, AdePeju Oshodi, Laura Heathers, Sean Teagarden, Li Wang, Alexander L Dent, Suthat Liangpunsakul
Background: Excessive drinkers (ED) and patients with alcoholic liver disease (ALD) are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations. Follicular helper T (TFH) cells are essential to select B cells in the germinal center and to produce antibodies. TFH cells express both a membrane-associated and a soluble form of CD40 ligand (sCD40L); in which the latter form is released to circulation upon T cell activation...
March 2018: Liver Research
Delphine Turpin, Adeline Furudoi, Marie Parrens, Patrick Blanco, Jean-François Viallard, Dorothée Duluc
Common variable immunodeficiency (CVID) is characterized by low levels of circulating immunoglobulins and defects in B cell maturation leading to an increased susceptibility to infections. Some patients develop complications such as autoimmune diseases, enteropathy, and lymphoproliferation, resulting in higher morbidity and mortality. Follicular helper T (Tfh) cells are specialized in helping B cell differentiation into Ig-producing cells. Three subsets have been described, namely non B-cell helper Tfh1 and the two B-helper cell subsets Tfh2 and Tfh17...
September 13, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Rebecca K Carrell, Rebecca A Stanton, Stephen P Ethier, Amanda C LaRue, Adam C Soloff
Cellular immunity established via immunotherapy holds the potential to eliminate solid tumors. Yet, cancer vaccines have failed to induce tumor-reactive T cells of sufficient quality to control disease. The inducible T cell costimulator (ICOS) pathway has been implicated in both the selective induction of immunity over tolerance as well as licensing of IL-17-polarized cellular immunity. Herein, we evaluated the ability of ICOS ligand (ICOSL) to augment the immunogenicity of adenoviral-based vaccination targeting the unglycosylated MUC1 peptide antigen...
September 12, 2018: Vaccine
Tue G Nguyen
Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common skin inflammatory conditions. B and T cells are strongly implicated in allergic contact hypersensitivity (CHS) conditions. Activation of IgD B-cell receptor (BCR) by anti-IgD stimulation depletes mature B cells and modulates T-helper cell type 1/2 (Th1/2) responses in vivo. It is not known whether these effects by anti-IgD exacerbates or ameliorates chronic skin inflammations. This study investigated the effects of anti-IgD and B-cell depleting anti-CD20 antibody on skin inflammation in CHS murine models...
September 12, 2018: Immunology Letters
Yanyan Yu, Leilei Wang, Guixiong Gu
Runx3, a member of the Runt-related transcription factor family, has attracted extensive attention due to its important role in the development of immune systems, especially in the differentiation of T cells. Accumulated evidence indicated that altered expression of Runx3 regulates a variety of target genes in different tissues/cells. Studies in animal models suggested that Runx3 may regulate the development of T cell lineage including those of innate lymphoid cells, Treg cells and dendritic cells, which may contribute to the development of hypersensitivity and asthma...
September 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Cancan Lyu, So Jin Bing, Wambui S Wandu, Biying Xu, Guangpu Shi, Samuel J Hinshaw, Mercedes Lobera, Rachel R Caspi, Lin Lu, Jianfei Yang, Igal Gery
EAU, an animal model for severe intraocular inflammatory eye diseases, is mediated by both Th1 and Th17 cells. Here, we examined the capacity of TMP778, a selective inhibitor of RORγt, to inhibit the development of EAU, as well as the related immune responses. EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Treatment with TMP778 significantly inhibited the development of EAU, determined by histological examination. In addition, the treatment suppressed the cellular immune response to IRBP, determined by reduced production of IL-17 and IFN-γ, as well as lower percentages of lymphocytes expressing these cytokines, as compared to vehicle-treated controls...
September 15, 2018: European Journal of Immunology
Stephanie M Rangel, Amy S Paller
Staphylococcus aureus infection is a major burden for individuals with moderate-to-severe atopic dermatitis and a known inducer of disease exacerbation. This increased susceptibility to staphylococcal infections has been attributed to abnormalities in the innate immune system of atopic dermatitis (AD) skin, including deficits in barrier proteins and lipids, and a muted response in generating antimicrobial peptides, all of which is further impaired by the activation of Th2 and Th22 immune pathways, which characterizes AD...
September 2018: Clinics in Dermatology
Patrícia Kellen Martins Oliveira-Brito, Maria Cristina Roque-Barreira, Thiago Aparecido da Silva
ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus , activates antigen-presenting cells by recognizing Toll-like receptor (TLR)2 and cluster of differentiation (CD)14 N -glycans, induces cytokine production, and promotes type 1 T helper (Th1) immunity, a process that plays an assisting role in the combat against fungal infections. We recently demonstrated that ArtinM stimulates CD4⁺ T cells to produce interleukin (IL)-17 through direct interaction with CD3. Here, we further investigated the effects of ArtinM on the production of IL-17 by B cell activation...
September 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Debaki R Howlader, Hemanta Koley, Ritam Sinha, Suhrid Maiti, Ushasi Bhaumik, Priyadarshini Mukherjee, Shanta Dutta
Salmonella Typhi and Salmonella Paratyphi A are the leading causative agents of enteric fever which cause morbidity and mortality worldwide. Currently, there is no combination vaccine which could protect infection from both the strains. In this paper, we are focusing on the development of a novel bivalent typhoidal Outer Membrane Vesicles (OMVs) based immunogen against enteric fever. We have isolated Salmonella Typhi and Paratyphi A OMVs and also characterized OMVs associated antigens. Then we immunized adult mice with three doses of our newly formulated bivalent immunogen orally (25 μg/200 μl)...
2018: PloS One
Grégory Ehx, Joan Somja, Hans-Jörg Warnatz, Caroline Ritacco, Muriel Hannon, Loïc Delens, Gilles Fransolet, Philippe Delvenne, Joséphine Muller, Yves Beguin, Hans Lehrach, Ludovic Belle, Stéphanie Humblet-Baron, Frédéric Baron
Despite the increasing use of humanized mouse models to study new approaches of graft-versus-host disease (GVHD) prevention, the pathogenesis of xenogeneic GVHD (xGVHD) in these models remains misunderstood. The aim of this study is to describe this pathogenesis in NOD/LtSz-Prkdcscid IL2rγtm1Wjl (NSG) mice infused with human PBMCs and to assess the impact of the expression of HLA-A0201 by NSG mice cells (NSG-HLA-A2/HHD mice) on xGVHD and graft-versus-leukemia (GvL) effects, by taking advantage of next-generation technologies...
2018: Frontiers in Immunology
Iris de Weerdt, Tom Hofland, Roeland Lameris, Sanne Endstra, Aldo Jongejan, Perry Moerland, Renee Cg de Bruin, Ester B M Remmerswaal, Ineke J M Ten Berge, Nora Liu, Mario van der Stelt, Laura M Faber, Mark-David Levin, Eric Eldering, Sanne H Tonino, Tanja D de Gruijl, Hans J van der Vliet, Arnon P Kater
The efficacy of autologous (αβ)-T cell-based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The Vγ9Vδ2T-cell subset comprises of cytotoxic T lymphocytes with potent anti-lymphoma activity via a major histocompatibility complex (MHC)-independent mechanism. We studied whether Vγ9Vδ2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control (HC) Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased frequency of the effector-type subset...
September 13, 2018: Blood
Hiroshi Arima, Momoko Nishikori, Yasuyuki Otsuka, Wataru Kishimoto, Kiyotaka Izumi, Koubun Yasuda, Tomohiro Yoshimoto, Akifumi Takaori-Kondo
The Notch-signaling pathway in a variety of mature B-cell neoplasms is often activated by gene alterations, but its role remains unclear. Here, we show that B cells harboring dysregulated activation of Notch1 signaling have an immunomodulatory effect on T cells by amplifying regulatory T (Treg) and T helper 2 (Th2) cell responses in an interleukin-33 (IL-33)-dependent manner. A conditional mouse model, in which constitutive expression of an active form of Notch1 is induced in B cells by Aicda gene promoter-driven Cre recombinase, revealed no obvious phenotypic changes in B cells; however, mice demonstrated an expansion of Treg and Th2 cell subsets and a decrease in cytokine production by Th1 and CD8+ T cells...
September 25, 2018: Blood Advances
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Musaad A Alshammari, Mohammad R Khan, Abdulaziz M S Alsaad, Sabry M Attia
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms include communication deficits, a lack of social skills, and stereotyped repetitive behaviors. We used BTBR T+ Itpr3tf /J (BTBR) mice, a model that demonstrates most of the core behavioral features of ASD, such as decreased sociability and high levels of repetitive behaviors. Currently, there is no treatment available that is able to improve most of the ASD disorder symptoms; thus, finding novel therapies is immediately required...
September 10, 2018: Cellular Signalling
Xueyun Zhao, Mingqiang Hua, Shuxin Yan, Jie Yu, Fengjiao Han, Chaoqin Zhong, Ruiqing Wang, Chen Zhang, Ming Hou, Daoxin Ma
The pathogenesis of multiple myeloma (MM) remains unclear and the NLRP3 inflammasome has been more and more recognized in the progression of many diseases. To investigate the role of the NLRP3 inflammasome in MM, we determined the genetic polymorphisms and expression of NLRP3 inflammasome-related genes (IL-1 β , IL-18, CARD8, and NF- κ B) in MM patients, and explored their clinical relevance. Furthermore, we investigated the relationship of the NLRP3 inflammasome with Th cells in MM. Our study showed that the CARD8-C10X (rs2043211) AT genotype contributed to the susceptibility of MM...
2018: Journal of Immunology Research
Zehua Zhang, Feifan Chen, Jianhua Li, Fei Luo, Tianyong Hou, Jianzhong Xu, Dong Sun
1,25(OH)2 D3 is an immune modulation hormone with beneficial effects on T cell- mediated autoimmune diseases. The purpose of the present study is to investigate the direct effects of vitamin D on Bacillus Calmette Guerin (BCG)-infected CD4+ T cells in both VDR-deficient (VDR-/-) mice and wild type (WT) mice. Specifically, we aimed to investigate the effect of vitamin D on Th1 cells and elucidate the underlying molecular mechanism. Naïve CD4 T cells were purified from VDR-/- mice and WT mice to induce Th1 cells and were activated by BCG...
2018: American Journal of Translational Research
Xiaoting Qu, Yuan Chen, Chaoyang Yin
The aim of this study was to investigate the effect of montelukast on the expression of CD4+ CD25+ regulatory T cells in children with acute bronchial asthma. Fifty-six child patients with acute bronchial asthma treated in the Department of Pneumology at the Shangluo Central Hospital were selected and randomly divided into the control group (n=28) and treatment group (n=28). The control group was treated with the conventional therapy of bronchial asthma, while the treatment group received montelukast on the basis of the control group for 7 days...
September 2018: Experimental and Therapeutic Medicine
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