MISC

査読有り 国際誌
2018年6月5日

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

Stem cell reports
  • Norihiro Ueda
  • ,
  • Yasushi Uemura
  • ,
  • Rong Zhang
  • ,
  • Shuichi Kitayama
  • ,
  • Shoichi Iriguchi
  • ,
  • Yohei Kawai
  • ,
  • Yutaka Yasui
  • ,
  • Minako Tatsumi
  • ,
  • Tatsuki Ueda
  • ,
  • Tian-Yi Liu
  • ,
  • Yasutaka Mizoro
  • ,
  • Chihiro Okada
  • ,
  • Akira Watanabe
  • ,
  • Mahito Nakanishi
  • ,
  • Satoru Senju
  • ,
  • Yasuharu Nishimura
  • ,
  • Kiyotaka Kuzushima
  • ,
  • Hitoshi Kiyoi
  • ,
  • Tomoki Naoe
  • ,
  • Shin Kaneko

10
6
開始ページ
1935
終了ページ
1946
記述言語
英語
掲載種別
DOI
10.1016/j.stemcr.2018.04.025

CD4+ T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40Lhigh iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40Lhigh iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia.

リンク情報
DOI
https://doi.org/10.1016/j.stemcr.2018.04.025
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29805109
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993651

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