In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response

Shimpei Kasagi, Pin Zhang, Li Che, Brittany Abbatiello, Takashi Maruyama, Hiroko Nakatsukasa, Peter Zanvit, Wenwen Jin, Joanne E. Konkel, Wan Jun Chen

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Harnessing regulatory T (Treg) cells is a promising approach for treating autoimmune disease. However, inducing antigen-specific Treg cells that target inflammatory immune cells without compromising beneficial immune responses has remained an unmet challenge. We developed a pathway to generate autoantigen-specific Treg cells in vivo, which showed therapeutic effects on experimental autoimmune encephalomyelitis and nonobese diabetes in mice. Specifically, we induced apoptosis of immune cells by systemic sublethal irradiation or depleted B and CD8+ T cells with specific antibodies and then administered autoantigenic peptides in mice with established autoimmune diseases. We demonstrated mechanistically that apoptotic cells triggered professional phagocytes to produce transforming growth factor-β, under which the autoantigenic peptides directed naïve CD4+ T cells to differentiate into Foxp3+ Treg cells instead of into T effector cells in vivo. These antigen-specific Treg cells specifically ameliorated autoimmunity without compromising immune responses to bacterial antigen. We have thus successfully generated antigen-specific T reg cells with therapeutic activity toward autoimmunity. The findings may lead to the development of antigen-specific Treg cell-mediated immunotherapy for multiple sclerosis and type 1 diabetes and also other autoimmune diseases.

Original languageEnglish
Article number241ra78
JournalScience Translational Medicine
Volume6
Issue number241
DOIs
Publication statusPublished - 2014 Jun 18
Externally publishedYes

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Regulatory T-Lymphocytes
Autoimmunity
Antigens
Autoimmune Diseases
Bacterial Antigens
T-Lymphocytes
Peptides
Autoimmune Experimental Encephalomyelitis
Viral Tumor Antigens
Transforming Growth Factors
Therapeutic Uses
Phagocytes
Type 1 Diabetes Mellitus
Immunotherapy
Multiple Sclerosis
Apoptosis
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response. / Kasagi, Shimpei; Zhang, Pin; Che, Li; Abbatiello, Brittany; Maruyama, Takashi; Nakatsukasa, Hiroko; Zanvit, Peter; Jin, Wenwen; Konkel, Joanne E.; Chen, Wan Jun.

In: Science Translational Medicine, Vol. 6, No. 241, 241ra78, 18.06.2014.

Research output: Contribution to journalArticle

Kasagi, Shimpei ; Zhang, Pin ; Che, Li ; Abbatiello, Brittany ; Maruyama, Takashi ; Nakatsukasa, Hiroko ; Zanvit, Peter ; Jin, Wenwen ; Konkel, Joanne E. ; Chen, Wan Jun. / In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response. In: Science Translational Medicine. 2014 ; Vol. 6, No. 241.
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