Ash Shifra, Yarkoni Shai, Askenasy Nadir
Frankel Laboratory, Department of Pediatric Hematology Oncology, Center for Stem Cell Research, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 49202, Petach Tikva, Israel.
Immunol Res. 2014 Jan;58(1):101-5. doi: 10.1007/s12026-013-8476-x.
One of the therapeutic approaches to type 1 diabetes (T1D) focuses on enhancement of regulatory T cell (Treg) activity, either by adoptive transfer or supplementation of supporting cytokines such as interleukin-2 (IL-2). In principle, this therapeutic design would greatly benefit of concomitant reduction in pathogenic cell burden. Experimental evidence indicates that physiological recovery from lymphopenia is dominated by evolution of effector and cytotoxic cells, which abolishes the therapeutic efficacy of Treg cells. Targeted and selective depletion of effector T cells has been achieved with killer Treg using Fas ligand protein and a fusion protein composed of IL-2 and caspase-3, which showed remarkable efficacy in modulating the course of inflammatory insulitis in NOD mice. We emphasize a critical consideration in design of therapeutic approaches to T1D, immunomodulation without lymphoreduction to avoid the detrimental consequences of rebound recovery from lymphopenia.
1型糖尿病（T1D）的一种治疗方法侧重于通过过继转移或补充支持性细胞因子（如白细胞介素-2（IL-2））来增强调节性T细胞（Treg）的活性。原则上，这种治疗设计将极大地受益于致病性细胞负荷的同时减少。实验证据表明，淋巴细胞减少后的生理恢复主要由效应细胞和细胞毒性细胞的演变主导，这消除了Treg细胞的治疗效果。使用Fas配体蛋白和由IL-2与半胱天冬酶-3组成的融合蛋白的杀伤性Treg已实现对效应T细胞的靶向和选择性清除，这在调节非肥胖糖尿病（NOD）小鼠的炎症性胰岛炎病程中显示出显著疗效。我们强调在设计T1D治疗方法时的一个关键考虑因素，即免疫调节而不进行淋巴细胞减少，以避免淋巴细胞减少后反弹恢复的有害后果。
