Journal Article iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells.

Cai, Songjie  ,  Hou, Jiangang  ,  Fujino, Masayuki  ,  Zhang, Qi  ,  Ichimaru, Naotsugu  ,  Takahara, Shiro  ,  Araki, Ryoko  ,  Ji-Mei, Chen  ,  Zhuang, Jian  ,  Zhu, Ping  ,  Xiao-Kang, Li

8 ( 5 )  , pp.1174 - 1189 , 2017-04
ISSN:2213-6711
Description
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2Kk) mice with B6 (H-2Kb) iPS-DCregs and found that Tregs (CD4+CD25+FOXP3+) significantly increased in CBA splenocytes. Moreover, immunized CBA recipients permanently accepted B6 cardiac grafts in a donor-specific pattern. We demonstrated mechanistically that donor-type iPS-DCregs triggered transforming growth factor β1 secretion, under which the donor-antigen peptides directed naive CD4+ T cells to differentiate into donor-specific FOXP3+ Tregs instead of into effector T cells in vivo. These findings highlight the potential of iPS-DCregs as a key cell therapy resource in clinical transplantation.

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