Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function

Regulatory T cells (Tregs) play a major role in the prevention of autoimmune diseases. Transfer of Foxp3 gene into conventional T cells converts their phenotype to regulatory T cells. Therefore, the question arises as to whether adoptively transferred in vitro differentiated Treg cells specific for...

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Main Authors: Mahdi Zavvar, Mohsen Abdolmaleki, Hamid Farajifard, Farshid Noorbakhsh, kayhan Azadmanesh, Mohammad Vojgani, Mohammad Hossein Nikcnam
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2018-08-01
Series:Iranian Journal of Allergy, Asthma and Immunology
Subjects:
Online Access:https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1609
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author Mahdi Zavvar
Mohsen Abdolmaleki
Hamid Farajifard
Farshid Noorbakhsh
kayhan Azadmanesh
Mohammad Vojgani
Mohammad Hossein Nikcnam
author_facet Mahdi Zavvar
Mohsen Abdolmaleki
Hamid Farajifard
Farshid Noorbakhsh
kayhan Azadmanesh
Mohammad Vojgani
Mohammad Hossein Nikcnam
author_sort Mahdi Zavvar
collection DOAJ
description Regulatory T cells (Tregs) play a major role in the prevention of autoimmune diseases. Transfer of Foxp3 gene into conventional T cells converts their phenotype to regulatory T cells. Therefore, the question arises as to whether adoptively transferred in vitro differentiated Treg cells specific for a locally expressed antigen might have better inhibitory effects on the progression of the disease as compared with antigen-nonspecific T reg cells. Herein, we investigated the therapeutic potential of primed and unprimed retrovirus mediated Foxp3-overexpression T cells following intravenously injected of these cells into affected rats with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. Our analyses demonstrate that systemic administration of collagen II primed Foxp3-transduced T cells could markedly ameliorate CIA inflammatory responses at clinical (p<0.0014) and pathological exchanges including cellular infiltration (p=0.002), bone erosion (p=0.0013) and synovial hyperplasia (p=0.002). In contrast, collagen II unprimed Foxp3-transduced T cells like as collagen II primed or unprimed GFP-transduced T cells did not reveal any beneficial effects on arthritis features as compared with untreated group (p>0.05). Therefore, we believe that collagen II primed Foxp3-transduced T cells are interacting locally and systemically with immune cells which reveled with decreasing of T cells infiltration into joints along with specific CII IgG production. Considering the results described here, it appears that the using patients' T cells which previously exposed to specific antigens may have more effective therapeutic advantage in the production of induced regulatory T cells in the treatment of arthritis.
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spelling doaj.art-11a266427cc642fb8b2066dabdcd5a1b2022-12-22T00:10:31ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492018-08-0117410.18502/ijaai.v17i4.951609Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell FunctionMahdi Zavvar0Mohsen Abdolmaleki1Hamid Farajifard2Farshid Noorbakhsh3kayhan Azadmanesh4Mohammad Vojgani5Mohammad Hossein Nikcnam6Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Virology, Pasteur Institute of Iran, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Molecular Immunology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, IranRegulatory T cells (Tregs) play a major role in the prevention of autoimmune diseases. Transfer of Foxp3 gene into conventional T cells converts their phenotype to regulatory T cells. Therefore, the question arises as to whether adoptively transferred in vitro differentiated Treg cells specific for a locally expressed antigen might have better inhibitory effects on the progression of the disease as compared with antigen-nonspecific T reg cells. Herein, we investigated the therapeutic potential of primed and unprimed retrovirus mediated Foxp3-overexpression T cells following intravenously injected of these cells into affected rats with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. Our analyses demonstrate that systemic administration of collagen II primed Foxp3-transduced T cells could markedly ameliorate CIA inflammatory responses at clinical (p<0.0014) and pathological exchanges including cellular infiltration (p=0.002), bone erosion (p=0.0013) and synovial hyperplasia (p=0.002). In contrast, collagen II unprimed Foxp3-transduced T cells like as collagen II primed or unprimed GFP-transduced T cells did not reveal any beneficial effects on arthritis features as compared with untreated group (p>0.05). Therefore, we believe that collagen II primed Foxp3-transduced T cells are interacting locally and systemically with immune cells which reveled with decreasing of T cells infiltration into joints along with specific CII IgG production. Considering the results described here, it appears that the using patients' T cells which previously exposed to specific antigens may have more effective therapeutic advantage in the production of induced regulatory T cells in the treatment of arthritis.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1609Collagen-induced arthritisRetroviral vectorsRheumatoid arthritisT regulatory cells
spellingShingle Mahdi Zavvar
Mohsen Abdolmaleki
Hamid Farajifard
Farshid Noorbakhsh
kayhan Azadmanesh
Mohammad Vojgani
Mohammad Hossein Nikcnam
Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
Iranian Journal of Allergy, Asthma and Immunology
Collagen-induced arthritis
Retroviral vectors
Rheumatoid arthritis
T regulatory cells
title Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
title_full Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
title_fullStr Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
title_full_unstemmed Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
title_short Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
title_sort collagen ii primed foxp3 transduced t cells ameliorate collagen induced arthritis in rats the effect of antigenic priming on t regulatory cell function
topic Collagen-induced arthritis
Retroviral vectors
Rheumatoid arthritis
T regulatory cells
url https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1609
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