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<p>In lung transplantation (LT), alloreactive T cell priming begins in the graft, a process that can be inhibited by seeding the graft with recipient-derived expanded polyclonal regulatory T cells (Tregs) using ex vivo lung perfusion (EVLP) prior to transplantation. However, this therapy alone cannot attenuate acute rejection in non-immunosuppressed animals. Interleukin 2 (IL-2)-anti-IL-2 antibody complexes (IL-2&#xa0;C) promote Treg expansion in vivo with concomitant tacrolimus (Tac) administration. We combined IL-2&#xa0;C and Tac with pre-transplant Treg administration during EVLP in a Fischer 344 to Wistar Kyoto rat LT model, to test the hypothesis that this strategy would facilitate intragraft Treg expansion and function. Recipients were given no treatment, Tac alone, IL-2&#xa0;C/Tac alone, Treg alone, or Treg/IL-2&#xa0;C/Tac. After 7 days, graft CD25<sup>high</sup>Foxp3<sup>+</sup> content increased as a result of Treg therapy, and cellular rejection was attenuated in the IL-2&#xa0;C/Tac and Treg/IL-2&#xa0;C/Tac groups. Graft Treg content and Treg-to-effector T cell ratio (Treg/Teff) at day 7 was highest in animals receiving Treg/IL-2&#xa0;C/Tac, which has important implications for long-term immunomodulation. Our data suggest that pre-transplant administration of graft-directed Treg cell therapy combined with Treg-permissive immunosuppression may be a viable therapeutic approach to modulate rejection in LT.</p>

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Permissive immunosuppression facilitates the expansion of ex vivo administered regulatory T cells in the lung allograft

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • Akihiro Takahagi,
  • Ei Miyamoto,
  • Christina Lam,
  • Mingyao Liu,
  • Betty Joe,
  • Xiaomin Wang,
  • David Hwang,
  • Tereza Martinu,
  • Marcelo Cypel,
  • Shaf Keshavjee,
  • Stephen Juvet

摘要

In lung transplantation (LT), alloreactive T cell priming begins in the graft, a process that can be inhibited by seeding the graft with recipient-derived expanded polyclonal regulatory T cells (Tregs) using ex vivo lung perfusion (EVLP) prior to transplantation. However, this therapy alone cannot attenuate acute rejection in non-immunosuppressed animals. Interleukin 2 (IL-2)-anti-IL-2 antibody complexes (IL-2 C) promote Treg expansion in vivo with concomitant tacrolimus (Tac) administration. We combined IL-2 C and Tac with pre-transplant Treg administration during EVLP in a Fischer 344 to Wistar Kyoto rat LT model, to test the hypothesis that this strategy would facilitate intragraft Treg expansion and function. Recipients were given no treatment, Tac alone, IL-2 C/Tac alone, Treg alone, or Treg/IL-2 C/Tac. After 7 days, graft CD25highFoxp3+ content increased as a result of Treg therapy, and cellular rejection was attenuated in the IL-2 C/Tac and Treg/IL-2 C/Tac groups. Graft Treg content and Treg-to-effector T cell ratio (Treg/Teff) at day 7 was highest in animals receiving Treg/IL-2 C/Tac, which has important implications for long-term immunomodulation. Our data suggest that pre-transplant administration of graft-directed Treg cell therapy combined with Treg-permissive immunosuppression may be a viable therapeutic approach to modulate rejection in LT.