Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes.
Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes.
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DOI：
10.3390/jcm10225306
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发表时间：
2021-11-15
影响因子：
3.9
通讯作者：
Marubashi S
中科院分区：
文献类型：
--
作者：
Sato N;Marubashi S
同种异体胰岛移植已经成为治疗因低血糖事件而导致意识障碍的严重1型糖尿病的有效选择。虽然目前的免疫抑制方案有效地防止了与受体初始T细胞激活相关的急性排斥反应，但慢性排斥反应仍然是实现长期同种异体胰岛植入的障碍。考虑到同种异体移植物具有克服慢性排斥反应的潜在能力，而不考虑维持免疫抑制的需要，这可能会对胰岛移植物产生毒性，因此发展对同种异体移植物的供者特异性免疫耐受是最终目标。最近，在非人类灵长类动物模型中，利用凋亡的供者淋巴细胞(ADL)诱导同种异体胰岛移植耐受的研究取得了突破性进展。一些研究表明，抗原特异性调节免疫网络的克隆性耗竭、无能和扩张是供者对ADLS耐受的机制，这些机制协同作用，诱导强大的移植耐受。这一成果标志着免疫耐受诱导的临床应用向前迈进了一大步。我们在此总结已报道的使用ADLS的胰岛移植的手术诱导疗法。此外，还讨论了胰岛移植的一些障碍，如胰岛的免疫原性和即刻血液介导的反应，这些都是今后需要解决的问题。
Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recipients, chronic rejection has remained an obstacle for achieving long-term allogeneic islet engraftment. The development of donor-specific immune tolerance to the allograft is the ultimate goal given its potential ability to overcome chronic rejection and disregard the need for maintenance immunosuppression, which may be toxic to islet grafts. Recently, a breakthrough in tolerance induction during allogeneic islet transplantation using apoptotic donor lymphocytes (ADLs) in a non-human primate model had been reported. Several studies have suggested that the clonal depletion, anergy, and expansion of the antigen-specific regulatory immune network are the mechanisms for donor-specific tolerance with ADLs, which act synergistically to induce robust transplant tolerance. This achievement represents a huge step forward toward the clinical application of immune tolerance induction. We herein summarize the reported operational induction therapies in islet transplantation using the ADLs. Moreover, a few obstacles for the engraftment of transplanted islets, such as islet immunogenicity and instant blood-mediated response, which need to be resolved in the future, are also discussed.
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影响因子：
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作者：
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DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1302771
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
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通讯作者：
Luo X