Immunosuppression by FK506 markedly prolongs expression of adenovirus-delivered transgene in skeletal muscles of adult dystrophic [mdx] mice.
Immunosuppression by FK506 markedly prolongs expression of adenovirus-delivered transgene in skeletal muscles of adult dystrophic [mdx] mice.
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FK506 的免疫抑制显着延长了成年营养不良 [mdx] 小鼠骨骼肌中腺病毒传递的转基因的表达。
DOI：
10.1006/bbrc.1995.2169
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发表时间：
1995
影响因子：
3.1
通讯作者：
G. Karpati
中科院分区：
文献类型：
--
作者：
Hanns Lochmüller;B. Petrof;C. Allen;S. Prescott;B. Massie;G. Karpati
腺病毒介导的成年免疫动物骨骼肌基因转移受到宿主对转导的肌肉纤维的细胞免疫攻击阻止长期转基因表达的事实的限制。在这项研究中，我们在腺病毒介导的报告基因转移后的10天和30天内，每天皮下注射免疫抑制药物FK506(他克莫司)治疗成年营养不良[MDX]小鼠，并将转导水平与生理盐水注射对照组进行比较。30天后，对照组不再有转基因表达，而FK506处理组的转基因表达保持在10天转导值的70%左右。此外，我们还发现免疫抑制组小鼠肌肉中CD3和CD8阳性T淋巴细胞的数量比对照组减少。
Adenovirus-mediated gene transfer into skeletal muscles of adult immune competent animals has been limited by the fact that a cellular immune attack of the host against transduced muscle fibers prevented long-term transgene expression. In this study we treated adult dystrophic [mdx] mice with daily subcutaneous injections of the immunosuppressive drug FK506 (tacrolimus) over 10 and 30 days after adenovirus-mediated reporter gene transfer and compared the transduction level to saline-injected controls. After 30 days, transgene expression was no longer demonstrable in the control group, whereas it remained at about 70% of the 10-day transduction value in the FK506 treated group. In addition, we demonstrated a reduction in the number of CD3 and CD8 positive T-lymphocytes in the muscles of the immunosuppressed group compared to controls.