Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 692, Rochester, NY 14610, USA.
J Immunol Methods. 2013 Dec 31;400-401:122-6. doi: 10.1016/j.jim.2013.10.010. Epub 2013 Nov 5.
The finding that murine and simian cells have differential susceptibility to diphtheria toxin (DTx) led to the development of genetically engineered mouse strains that express the simian or human diphtheria toxin receptor (DTR) under the control of various mouse gene promoters. Injection of DTx into DTR engineered mice allows for rapid and transient depletion of various cell populations. There are several advantages to this approach over global knockout mice, including normal mouse development and temporal control over when cell depletion occurs. As a result, many DTR engineered mouse strains have been developed, resulting in significant insights into the cell biology of various disease states. We used Foxp3(DTR) mice to attempt local depletion of Foxp3+ cells in the lung in a model of tolerance breakdown. Intratracheal administration of DTx resulted in robust depletion of lung Foxp3+ cells. However, DTx administration was accompanied by significant local inflammation, even in control C57Bl/6 mice. These data suggest that DTx administration to non-transgenic mice is not always an immunologically inert event, and proper controls must be used to assess various DTx-mediated depletion regimens.
研究发现，鼠类和灵长类细胞对白喉毒素（DTx）的敏感性不同，这导致了基因工程小鼠品系的发展，这些小鼠品系在各种小鼠基因启动子的控制下表达灵长类或人类白喉毒素受体（DTR）。将 DTx 注射到 DTR 工程小鼠中，可以快速、短暂地耗尽各种细胞群。与全局敲除小鼠相比，这种方法有几个优点，包括正常的小鼠发育和对细胞耗竭发生时间的时间控制。因此，已经开发了许多 DTR 工程小鼠品系，这为各种疾病状态的细胞生物学提供了重要的见解。我们使用 Foxp3(DTR) 小鼠试图在耐受破裂模型中局部耗尽肺部的 Foxp3+细胞。气管内给予 DTx 导致肺部 Foxp3+细胞的大量耗竭。然而，即使在对照 C57Bl/6 小鼠中，DTx 给药也伴随着明显的局部炎症。这些数据表明，DTx 给药给非转基因小鼠并不总是一种免疫惰性事件，必须使用适当的对照来评估各种 DTx 介导的耗竭方案。
