FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development

Rizwanul Haque, Fengyang Lei, Xiaofang Xiong, Yuzhang Wu, Jianxun Song

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Introduction: Forkhead box p3 (FoxP3)-expressing regulatory T cells (Tregs) have been clearly implicated in the control of autoimmune disease in murine models. In addition, ectopic expression of FoxP3 conveys a Treg phenotype to CD4+ T cells, lending itself to therapeutic use in the prevention of rheumatoid arthritis (RA). In this study, we generated therapeutically active Tregs with an increased life span and hence greater therapeutic potential.Methods: We used retrovirus-mediated transduction to introduce FoxP3 or FoxP3 with anti-apoptotic Bcl-2 family molecule Bcl-xL linked by a 2A picornavirus self-cleaving peptide into CD4+ T cells to generate Tregs. In addition, by using in vitro functional analyses and adoptive immunotherapy in a murine model of RA, we demonstrated that these Tregs were highly reactive.Results: We found that CD4+ T cells expressing both FoxP3 and Bcl-xL were able to differentiate into functional Tregs, which have a long-term survival advantage over cells transduced with FoxP3 alone. In an in vivo murine model, adoptive transfer of Tregs expressing both FoxP3 and Bcl-xL demonstrated more effective suppression of RA than CD4+ T cells expressing FoxP3 alone.Conclusions: FoxP3 and Bcl-xL can cooperatively promote the differentiation and persistence of Tregs, with the capacity to prevent arthritis. Our results provide a novel approach for generating highly reactive Tregs for augmenting cellular immunotherapy for autoimmune disease.

Original languageEnglish (US)
Article numberR66
JournalArthritis Research and Therapy
Volume12
Issue number2
DOIs
StatePublished - Apr 12 2010

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Regulatory T-Lymphocytes
Arthritis
T-Lymphocytes
Rheumatoid Arthritis
Autoimmune Diseases
Picornaviridae
Adoptive Immunotherapy
Adoptive Transfer
Therapeutic Uses
Retroviridae
Immunotherapy
Phenotype
Peptides
Therapeutics

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Haque, Rizwanul ; Lei, Fengyang ; Xiong, Xiaofang ; Wu, Yuzhang ; Song, Jianxun. / FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. In: Arthritis Research and Therapy. 2010 ; Vol. 12, No. 2.
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FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. / Haque, Rizwanul; Lei, Fengyang; Xiong, Xiaofang; Wu, Yuzhang; Song, Jianxun.

In: Arthritis Research and Therapy, Vol. 12, No. 2, R66, 12.04.2010.

Research output: Contribution to journalArticle

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