The depletion of Foxp3+/CD25+ regulatory T cells drives a Th2 immune response and reduces severity in a mouse model of acute pancreatitis.

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S26
Author(s):  
Juliane Glaubitz ◽  
Anika Wilden ◽  
Cindy van den Brandt ◽  
Frank Ulrich Weiss ◽  
Julia Mayerle ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Acute Pancreatitis ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Th2 Immune Response

Aggregate content influences the Th1/Th2 immune response to influenza vaccine: Evidence from a mouse model

2003 ◽  
Vol 72 (1) ◽  
pp. 138-142 ◽  
Author(s):  
Shawn Babiuk ◽  
Danuta M. Skowronski ◽  
Gaston De Serres ◽  
Kent HayGlass ◽  
Robert C. Brunham ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Influenza Vaccine ◽  
Aggregate Content ◽  
Th2 Immune Response

scholarly journals CD4+CD25+Foxp3+ regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052098094
Author(s):  
Shuang Qin ◽  
Li Li ◽  
Jia Liu ◽  
Jinrui Zhang ◽  
Qing Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Tlr4 Antagonist

Objective The present study aimed to evaluate the effects of cluster of differentiation (CD)4+CD25+ forkhead box p3 (Foxp3)+ regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. Methods The proportion of CD4+CD25+Foxp3+ Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. Results The proportion of CD4+CD25+Foxp3+ Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4+CD25+Foxp3+ Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. Conclusions These data suggest that CD4+CD25+Foxp3+ Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.

scholarly journals 873 Pharmacologic macrophage depletion affects metastasis formation by modulating systemic immune responses in a genetic pancreatic cancer model

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A926-A926
Author(s):  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Christof Drexel ◽  
Nada Milosevic ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Immune Cells ◽  
Tumour Progression ◽  
Metastasis Formation ◽  
Macrophage Depletion ◽  
Genetic Mouse Model ◽  
Liposomal Clodronate

BackgroundTumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias and are known to mediate tumour progression.MethodsWe aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in the genetic mouse model of pancreatic cancer (KPC mouse: LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre). KPC mice were treated with liposomal clodronate or control liposomes from week 8 to week 20. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.ResultsTreatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. Tumour incidence and size was only slightly reduced. However, metastasis formation in the liver und lungs was markedly diminished after macrophage depletion. Reduced macrophage count was associated with significant alterations in circulating growth factors and mediators known to be secreted by macrophages and associated with angiogenesis, most prominently VEGF. Moreover, application of liposomal clodronate led to marked alterations in circulating immune cells, among them reduced regulatory T cells.ConclusionsPharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with modulated profile of both secreted mediators and regulatory T cells. Pharmacological modulation of infiltrating macrophages represents a promising avenue for antimetastatic therapeutic approaches.

scholarly journals Characteristics of Regulatory T cells

2016 ◽  
Vol 85 (4) ◽  
pp. 323-326
Author(s):  
Magdalena Frydrychowicz ◽  
Maciej Boruczkowski ◽  
Agata Kolecka-Bednarczyk ◽  
Renata Jenek ◽  
Joanna Rosołowska ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Adhesion Molecules ◽  
Chemokine Receptors ◽  
Toll Like Receptors ◽  
Effector Cells

Regulatory T cells (Tregs) is heterogenic subpopulation of T cells that is able to suppress function of effector cells during the immune response. Among them are natural (nTreg) and induced Treg (Tr1, Th3, CD4+CD25-). CD25, CD45Ro, CD152, GITR, LAG-3, several adhesion molecules, chemokine receptors as well as Toll-like receptors are present on the surface of Treg. Mechanism of suppression used by nTreg is not completely understood.

scholarly journals Therapeutic efficacy of an immune stimulatory gene therapy strategy in a mouse model of high grade brainstem glioma

2019 ◽  
Author(s):  
Flor M. Mendez ◽  
Padma Kadiyala ◽  
Felipe J. Nunez ◽  
Stephen Carney ◽  
Fernando Nunez ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
T Cells ◽  
Mouse Model ◽  
Tyrosine Kinase ◽  
Thymidine Kinase ◽  
Tumor Antigen ◽  
Therapeutic Efficacy ◽  
Brainstem Glioma ◽  
Adenoviral Delivery

AbstractPurposeDiffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, ACVR1-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy.Experimental DesignWe utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNAseq analysis on neurospheres (NS) harboring mACVR1. mACVR1 NS were implanted into the pons of immune competent mice to test the therapeutic efficacy and toxicity of immune stimulatory gene therapy using adenoviruses expressing thymidine kinase (TK) and fms-like tyrosine kinase 3 ligand (Flt3L). mACVR1 NS expressing the surrogate tumor antigen ovalbumin were generated to investigate if TK/Flt3L treatment induces the recruitment of tumor-antigen specific T cells.ResultsHistological analysis of mACVR1 tumors indicates that they are localized in the brainstem and have increased downstream signaling of bone morphogenetic pathway as demonstrated by increased phospho-smad1/5 and Id1 levels. Transcriptome analysis of mACVR1 NS identified an increase in the transforming growth factor beta (TGF-β) signaling pathway and the regulation of cell differentiation. Adenoviral delivery of TK/Flt3L in mice bearing brainstem gliomas resulted in anti-tumor immunity, recruitment of anti-tumor specific T cells and increased median survival.ConclusionsThis study provides insights into the phenotype and function of the tumor immune microenvironment in a mouse model of brainstem glioma harboring mACVR1. Immune stimulatory gene therapy targeting the hosts’ anti-tumor immune response inhibits tumor progression and increases median survival of mice bearing mACVR1 tumors.Translational RelevanceThe therapeutic efficacy of anti-DIPG immune responses is limited due to a low number of immune cells in the tumor microenvironment. We have uncovered a novel treatment strategy that utilizes adenoviral delivery of therapeutic genes, thymidine kinase (TK) and fms tyrosine kinase 3 ligand (Flt3L) into the tumor, eliciting a reprograming of the host’s own immune system to recognize and kill tumor cells. We demonstrate that TK/Flt3L therapy generates an effective anti-tumor response and can be safely delivered into the brainstem. This treatment approach could provide a novel translational approach towards potentiating an anti-DIPG immune response to overcome the current limitations in the treatment of patients with DIPG.

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