Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4⁺CD25⁺FoxP3⁺ T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

胰岛移植是治疗1型糖尿病的有前途的疗法。但是，控制异基因胰岛排斥反应的慢性免疫抑制会引起发病并损害胰岛功能。T效应细胞负责同种异体胰岛排斥反应，并在激活后表达Fas死亡受体，对Fas介导的细胞凋亡变得敏感。在这里，我们报告使用局部免疫调节使用微凝胶呈现与链霉亲和素（SA-FasL）的凋亡形式的Fas配体导致糖尿病小鼠异基因胰岛移植物的存活时间延长。雷帕霉素的短期治疗提高了SA-FasL微凝胶的免疫调节功效，导致同种异体移植在200天内被接受并发挥了作用。幸存者对供体抗原产生正常的全身反应，这意味着移植物具有免疫特权，并具有增加的CD4⁺ CD25 ⁺ FoxP3 ⁺ T调节细胞在移植和引流淋巴结中。T调节细胞的删除导致已建立的胰岛同种异体移植物的急性排斥。这种局部免疫调节生物材料支持的方法可以为临床胰岛移植提供慢性免疫抑制的替代方法。