学術雑誌論文 Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response

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

102018-05-24 , Elsevier BV
ISSN:2213-6711
内容記述
ヒトiPS細胞由来T細胞に遺伝子を導入すると、ヘルパーT細胞様の機能を獲得することを発見しました. 京都大学プレスリリース. 2018-06-04.
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.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/231323/1/j.stemcr.2018.04.025.pdf

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