Systemic immunological effects of cytokine genes injected into skeletal muscle.
Systemic immunological effects of cytokine genes injected into skeletal muscle.
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注射到骨骼肌中的细胞因子基因的全身免疫效应。
DOI：
10.1073/pnas.90.10.4523
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发表时间：
1993
影响因子：
11.1
通讯作者：
Carson,DA
中科院分区：
文献类型：
--
作者：
Raz,E;Watanabe,A;Baird,SM;Eisenberg,RA;Parr,TB;Lotz,M;Kipps,TJ;Carson,DA
体细胞基因治疗是一种有趣的长时间输送细胞因子的方法。目前的实验表明，将编码白介素2(IL-2)、白介素4(IL-4)或β1转化生长因子(TGF-β1)的基因表达载体直接注射到小鼠骨骼肌内，可在体内诱导这些细胞因子特有的生物学效应。肌肉注射编码IL-2的载体的小鼠增强了对外源抗原转铁蛋白的体液和细胞免疫反应，转铁蛋白是在一个单独的部位传递的。这些IL-2效应被联合应用指导合成转化生长因子-β1的载体所消除。转化生长因子-β1载体本身抑制抗转铁蛋白抗体反应，并导致血浆转化生长因子-β1活性增加8倍。注射转化生长因子-β1质粒未引起肌肉中单核细胞或中性粒细胞的渗入，也没有纤维化改变的证据。肌肉注射编码IL-4的cDNA选择性地增加IgG1水平，但不改变对转铁蛋白的细胞免疫反应。在狼疮易感小鼠(MRL/LPR/LPR)中，注射IL-2表达载体的小鼠增加了对染色质的自身抗体，而注射转化生长因子-β1载体的小鼠的自身抗体减少。这些结果表明，在没有感染性病毒载体的情况下，肌肉注射细胞因子基因可以调节体内的体液和细胞免疫反应。
Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF-beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF-beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo.