論文

国際誌
2023年5月22日

Calcineurin inhibitor inhibits tolerance induction by suppressing terminal exhaustion of donor T cells after allo-HCT.

Blood
  • Hajime Senjo
  • Shinpei Harada
  • Shimpei I Kubota
  • Yuki Tanaka
  • Takahiro Tateno
  • Zixuan Zhang
  • Satomi Okada
  • Xuanzhong Chen
  • Ryo Kikuchi
  • Naoki Miyashita
  • Masahiro Onozawa
  • Hideki Goto
  • Tomoyuki Endo
  • Yuta Hasegawa
  • Hiroyuki Ohigashi
  • Takahide Ara
  • Yoshinori Hasegawa
  • Masaaki Murakami
  • Takanori Teshima
  • Daigo Hashimoto
  • 全て表示

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1182/blood.2023019875

Calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis is standard in allogeneic hematopoietic stem cell transplantation (HCT) but fails to induce long-term tolerance without chronic GVHD in a considerable number of patients. In this study, we addressed this long-standing question in mouse models of HCT. After HCT, alloreactive donor T cells rapidly differentiated into PD-1+ TIGIT+ terminally exhausted T cells (terminal-Tex). GVHD prophylaxis with cyclosporine (CSP) suppressed donor T-cell expression of TOX, a master regulator to promote differentiation of transitory exhausted T cells (transitory-Tex), expressing both inhibitory receptors and effector molecules, into terminal-Tex, and inhibited tolerance induction. Adoptive transfer of transitory-Tex, but not terminal-Tex, into secondary recipients developed chronic GVHD. Transitory-Tex maintained alloreactivity and thus PD-1 blockade restored graft-versus-leukemia (GVL) activity of transitory-Tex, not terminal-Tex. In conclusion, CSP inhibits tolerance induction by suppressing the terminal exhaustion of donor T cells, while maintaining GVL effects to suppress leukemia relapse.

リンク情報
DOI
https://doi.org/10.1182/blood.2023019875
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/37216687
ID情報
  • DOI : 10.1182/blood.2023019875
  • PubMed ID : 37216687

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