PDF(Pubmed)
Abstract：
BACKGROUND: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.
METHODS: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients. By utilizing an immunogenic skin transplant model and existing transplantation medicine reagents, we facilitated the clinical translation of our findings. Specifically, antigen-specific Tregs were used.
RESULTS: Our study demonstrated that combining the available induction therapies with drug-induced T-cell proliferation due to lymphopenia effectively increased the Treg/T effector ratios. This results in significant Treg accumulation within the graft, leading to long-term tolerance after the transfer of antigen-specific Tregs. Importantly, all the animals achieved operational tolerance, which boosted the presence of adoptively transferred Tregs within the graft.
CONCLUSIONS: This protocol offers a means to establish tolerance by utilizing antigen-specific Tregs. These results have promising implications for future trials involving adoptive Treg therapy in organ transplantation.
METHODS: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients. By utilizing an immunogenic skin transplant model and existing transplantation medicine reagents, we facilitated the clinical translation of our findings. Specifically, antigen-specific Tregs were used.
RESULTS: Our study demonstrated that combining the available induction therapies with drug-induced T-cell proliferation due to lymphopenia effectively increased the Treg/T effector ratios. This results in significant Treg accumulation within the graft, leading to long-term tolerance after the transfer of antigen-specific Tregs. Importantly, all the animals achieved operational tolerance, which boosted the presence of adoptively transferred Tregs within the graft.
CONCLUSIONS: This protocol offers a means to establish tolerance by utilizing antigen-specific Tregs. These results have promising implications for future trials involving adoptive Treg therapy in organ transplantation.
摘要：
背景：实体器官移植受到免疫介导的慢性移植物功能障碍和免疫抑制治疗副作用的阻碍。调节性T细胞（Tregs）对于调节移植后的免疫反应至关重要；然而，仅多特异性Treg的转移不足以在啮齿动物模型中诱导同种异体耐受性。
方法：为了提高过继性Treg治疗的疗效，我们调查了受者的不同免疫干预措施.通过利用免疫原性皮肤移植模型和现有的移植药物试剂，我们促进了我们发现的临床翻译.具体来说,使用抗原特异性Tregs。
结果：我们的研究表明，将可用的诱导疗法与由于淋巴细胞减少引起的药物诱导的T细胞增殖相结合，可以有效地增加Treg/T效应子比率。这导致移植物内明显的Treg积累，导致抗原特异性Tregs转移后的长期耐受性。重要的是,所有动物都达到了操作耐受性，这增加了移植体内过继转移的Tregs的存在。
结论：该方案提供了一种通过利用抗原特异性Treg建立耐受性的方法。这些结果对器官移植中涉及过继性Treg疗法的未来试验具有有希望的意义。
方法：为了提高过继性Treg治疗的疗效，我们调查了受者的不同免疫干预措施.通过利用免疫原性皮肤移植模型和现有的移植药物试剂，我们促进了我们发现的临床翻译.具体来说,使用抗原特异性Tregs。
结果：我们的研究表明，将可用的诱导疗法与由于淋巴细胞减少引起的药物诱导的T细胞增殖相结合，可以有效地增加Treg/T效应子比率。这导致移植物内明显的Treg积累，导致抗原特异性Tregs转移后的长期耐受性。重要的是,所有动物都达到了操作耐受性，这增加了移植体内过继转移的Tregs的存在。
结论：该方案提供了一种通过利用抗原特异性Treg建立耐受性的方法。这些结果对器官移植中涉及过继性Treg疗法的未来试验具有有希望的意义。
