Transgene-specific host responses in cutaneous gene therapy: the role of cells expressing the transgene.
Transgene-specific host responses in cutaneous gene therapy: the role of cells expressing the transgene.
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作者：
长期基因治疗的一个主要问题是当转基因编码潜在的抗原时，宿主对治疗细胞的免疫反应。这些反应的性质取决于几个因素，包括表达转基因的细胞和组织的类型。角质形成细胞和成纤维细胞具有不同的免疫原性，它们都是皮肤基因治疗中转基因表达的潜在靶点。然而，靶向一种类型的细胞是否比另一种类型的细胞具有免疫学优势尚不清楚。为了研究细胞类型对转基因特异性宿主反应的影响，不依赖于抗原水平或基因转移和移植的方法，我们使用了一种皮肤移植模型，在该模型中，转基因表达可以靶向转基因角质形成细胞或成纤维细胞。尽管针对任何一种细胞类型的抗原都会导致免疫反应的诱导，但这些反应明显不同。转基因角质形成细胞受到Th2反应的强烈排斥，而在大多数移植动物中，转基因成纤维细胞未能诱导急性排斥反应，尽管在移植物中诱导了Th1型炎症。在少数小鼠中，转基因成纤维细胞至少持续了20周，尽管引发了抗原特异性反应。因此，与角质形成细胞相比，成纤维细胞可能是皮肤基因治疗的免疫首选靶点。
A major issue in long-term gene therapy is host immune responses to therapeutic cells when transgene encodes a potential antigen. The nature of these responses depends on several factors including the type of cell and tissue expressing the transgene. Keratinocytes and fibroblasts, which are known to display distinct immunogenic profiles, are both potential targets for transgene expression in cutaneous gene therapy. However, whether there is an immunological advantage in targeting one cell type over the other is not known. To study the effect of cell type on transgene-specific host responses independent of antigen levels or methods of gene transfer and transplantation, we used a skin transplantation model in which transgene expression can be targeted transgene to either keratinocytes or fibroblasts. Although targeting an antigen to either cell type resulted in the induction of immune responses, these responses differed significantly. Transgenic keratinocytes were rejected acutely by a dominant Th2 response, while in the majority of grafted animals transgenic fibroblasts failed to induce acute rejection despite the induction of Th1 type inflammation in the graft. In a small number of mice, transgenic fibroblasts persisted for at least 20 weeks despite elicitation of antigen-specific responses. Therefore, fibroblasts may be an immunologically preferred target over keratinocytes for cutaneous gene therapy.
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DOI：
10.1097/00004630-198903000-00009
发表时间：
1989-03-01
期刊：
The Journal of burn care & rehabilitation
影响因子：
--
作者：
Lerner-Tung, M B;Hull, B E
通讯作者：
Hull, B E
影响因子：
3.6
作者：
Lu, Z;Ghazizadeh, S
通讯作者：
Ghazizadeh, S
影响因子：
12.4
作者：
Lu, Zhenmei;Ghazizadeh, Soosan
通讯作者：
Ghazizadeh, Soosan
影响因子：
4.4
作者：
Haniffa, Muzlifah A.;Wang, Xiao-Nong;Collin, Matthew P.
通讯作者：
Collin, Matthew P.
影响因子：
82.9
作者：
Condon, C;Watkins, SC;Falo, LD
通讯作者：
Falo, LD