scholarly journals 468. Cellular Therapy with Transgene Expressing APC Activates CD4 + CD25+ Regulatory T Cells Which Modulate the Immune Response to Gene Therapy Derived Products in Immunocompetent Mice

2005 ◽  
Vol 11 ◽  
pp. S181-S182
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cellular Therapy ◽  
Immunocompetent Mice

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.

In Vivo-Generated Antigen-Specific Regulatory T Cells Treat Autoimmunity Without Compromising Antibacterial Immune Response

2014 ◽  
Vol 6 (241) ◽  
pp. 241ra78-241ra78 ◽  
Author(s):  
S. Kasagi ◽  
P. Zhang ◽  
L. Che ◽  
B. Abbatiello ◽  
T. Maruyama ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells

scholarly journals Platelet Gene Therapy Promotes Targeted Peripheral Tolerance by Clonal Deletion and Induction of Antigen-Specific Regulatory T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Xiaofeng Luo ◽  
Juan Chen ◽  
Jocelyn A. Schroeder ◽  
Kenneth P. Allen ◽  
Christina K. Baumgartner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Tolerance ◽  
Clonal Deletion

Analysis of regulatory T cells and CTLA-4 expression in pregnant women according to seropositivity to Toxoplasma gondii

Parasitology ◽  
2020 ◽  
Vol 147 (7) ◽  
pp. 810-815
Author(s):  
Karine Rezende-Oliveira ◽  
César Gómez-Hernández ◽  
Marcos Vinicius da Silva ◽  
Fernanda Rodrigues Helmo ◽  
Virmondes Rodrigues
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Toxoplasma Gondii ◽  
Regulatory T Cells ◽  
Pregnant Women ◽  
Positive Serology ◽  
Surface Molecules

AbstractPregnancy is considered a period in which immunomodulation occurs, although it is important for the maintenance of the foetus, could contribute to infections as Toxoplasma gondii. Immune response cells such as regulatory T cells participate in this immunomodulation, and surface molecules such as CTLA-4 develop an immunosuppressive role, could contribute to the establishment of the parasite. This study aimed to evaluate the presence of regulatory T cells and the expression of CTLA-4 in parturient and non-pregnant seropositive and seronegative for anti-T. gondii antibodies. Sixty-two participants were evaluated, 14 parturient with negative serology, 23 parturient with positive serology, 16 non-pregnant women seronegative and 9 non-pregnant women seropositive. Immunophenotyping was performed for characterize TCD4+Foxp3+ cells, T CD4+CD25-Foxp3+, TCD4+CD25highFoxp3+, TCD4+CTLA-4+, TCD4+CD25-CTLA-4+ and TCD4+CD25highCTLA-4+. We observed a lower level of CD4+CD25highFoxp3+ cells from seropositive parturient compared with seropositive non-pregnant cells. Significative levels of CD4+CD25-Foxp3+ cells from seronegative pregnant were observed compared with seropositive pregnant cells. Furthermore, the higher level of CD4+CD25-CTLA-4+ cells populations was detected in seropositive pregnant cells compared with seropositive non-pregnant. Although a significant increase in CTLA-4 cells was observed in pregnant women positive for anti-T. gondii antibodies, this increase did not cause a risk of reactivation of the infection.

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