Regulatory T cells and immune tolerance to coagulation factor IX in the context of intramuscular AAV1 gene transfer.
Regulatory T cells and immune tolerance to coagulation factor IX in the context of intramuscular AAV1 gene transfer.
复制标题
肌内 AAV1 基因转移背景下的调节性 T 细胞和对凝血因子 IX 的免疫耐受。
DOI：
10.1038/mt.2009.269
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Chao,Hengjun
中科院分区：
文献类型：
--
作者：
Kelly,Meagan;Bharadwaj,ArpitaS;Tacke,Frank;Chao,Hengjun
调节性T细胞在诱导和维持免疫耐受和免疫稳态中起主要作用。已经尝试了多种策略来诱导调节性T细胞，以控制自身免疫性疾病、移植以及基因转移中不需要的不良免疫。我们最近报道了肌内AAV 1基因转移后对凝血因子IX（FIX）的免疫耐受的有效诱导。在本研究中，我们对调节性T细胞在肌内AAV 1基因转移背景下诱导和维持FIX耐受性中的作用和功能进行了系统和全面的检查。我们观察到Fix耐受小鼠中调节性T细胞没有显着上调。此外，从FIX耐受小鼠过继转移脾细胞不会抑制受体小鼠的抗hFIX免疫。调节性T细胞的体外和体内耗竭均未能逆转FIX耐受。这些观察结果表明，调节性T细胞在维持/保护已建立的FIX耐受性方面不起显著作用。我们的研究结果提供了关键的洞察调节性T细胞在诱导和维持/保护基因转移免疫耐受的作用和功能，补充了目前的免疫耐受机制的范例。
Regulatory T cells play a major role in induction and maintenance of immune tolerance and immunological homeostasis. A variety of strategies have been attempted to induce regulatory T cells for control of unwanted, adverse immunity in autoimmune diseases, transplantation as well as gene transfer. We recently reported efficient induction of immune tolerance to coagulation factor IX (FIX) following intramuscular AAV1 gene transfer. In the current study, we performed a systematic and comprehensive examination of the role and function of regulatory T cells in induction and maintenance of FIX tolerance in the context of intramuscular AAV1 gene transfer. We observed no significant upregulation of regulatory T cells in the FIX-tolerant mice. In addition, adoptive transfer of splenocytes from FIX-tolerant mice did not suppress anti-hFIX immunity in recipient mice. Bothin vitroandin vivodepletion of regulatory T cells failed to reverse FIX tolerance. These observations revealed that regulatory T cells do not play a significant role in the maintenance/protection of the established FIX tolerance. Our results provide critical insight into the role and function of regulatory T cells in induction and maintenance/protection of immune tolerance in gene transfer, complementing the current paradigm of immune tolerance mechanism.