重复长期 DT 应用于 DEREG 小鼠诱导中和抗 DT 抗体反应。
Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response.
机构信息
Institute of Parasitology, University of Bern, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
出版信息
J Immunol Res. 2016;2016:1450398. doi: 10.1155/2016/1450398. Epub 2016 Dec 15.
Regulatory T (Tregs) cells play an important role in mediating tolerance to self-antigens but can also mediate detrimental tolerance to tumours and pathogens in a Foxp3-dependent manner. Genetic tools exploiting the locus including bacterial artificial chromosome- (BAC-) transgenic DEpletion of REGulatory T cells (DEREG) mice have provided essential information on Treg biology and the potential therapeutic modulation of tolerance. In DEREG mice, Foxp3 Tregs selectively express enhanced green fluorescent protein (eGFP) and diphtheria toxin (DT) receptor, allowing for the specific depletion of Tregs through DT administration. We here provide a detailed overview about an important consideration that long-term administration of DT induces a humoral immune response with an appropriate production of anti-DT antibodies that can inactivate DT and thus abrogate its effect in the DEREG mouse. Additionally, we showed that anti-DT mouse serum partially neutralized DT-induced Foxp3 inhibition.
调节性 T（Treg）细胞在介导对自身抗原的耐受方面发挥着重要作用，但也可以通过 Foxp3 依赖性方式介导对肿瘤和病原体的有害耐受。利用包括细菌人工染色体-（BAC）转基因 DEpletion of REGulatory T cells（DEREG）小鼠在内的 座的遗传工具，为 Treg 生物学和耐受的潜在治疗调节提供了重要信息。在 DEREG 小鼠中，Foxp3 Tregs 选择性地表达增强型绿色荧光蛋白（eGFP）和白喉毒素（DT）受体，通过给予 DT 可以特异性耗竭 Tregs。我们在此提供了一个重要考虑因素的详细概述，即 DT 的长期给药会诱导产生针对白喉毒素的体液免疫反应，从而产生适当的抗 DT 抗体，这些抗体可以使 DT 失活，从而在 DEREG 小鼠中消除其作用。此外，我们还表明，抗 DT 鼠血清部分中和了 DT 诱导的 Foxp3 抑制。
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