Functional study of immature dendritic cells co-transfected with IL-10 and TGF-beta 1 genes in vitro

Functional study of immature dendritic cells co-transfected with IL-10 and TGF-beta 1 genes in vitro
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DOI:
10.1007/s11033-012-1468-4
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发表时间:
2012-06-01
影响因子:
2.8
通讯作者:
Liu, Jingfeng
Liu, Jingfeng
中科院分区:
生物学4区
文献类型:
--
作者:
Chen, Lihong;Qiu, Minglian;Liu, Jingfeng

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树突状细胞(DC)在T细胞免疫和T细胞耐受中发挥重要作用。以往的研究表明,未成熟的树突状细胞(ImDC)可能参与了外周T细胞耐受的诱导。虽然白介素10(IL-10)在不同水平的免疫应答中发挥作用,但转化生长因子-β1(TGF-β1)被认为是免疫耐受的关键因素。本研究探讨IL-10和转化生长因子-β1基因共转染未成熟树突状细胞(IMDC)诱导免疫耐受的作用。此外,我们还比较了IL-10-转化生长因子-β1-iMDC(IL-10-IMDC)和转化生长因子-β1-iMDC(转化生长因子-β1-iMDC)的作用。IL-10-TGF-β1-IMDC可下调MHC-II、CD80和CD86的表达。IL-10-转化生长因子-β1-IMDC可诱导T细胞低反应性,且不愿增殖。IL-10-TGF-β1-IMDC较IL-10-IMDC和转化生长因子-β1-IMDC更有效。综上所述,IL-10和转化生长因子-β1的共同表达影响了imDC的免疫功能,增强了其耐受性。它可能是治疗器官移植后供者特异性耐受的一种有前途的治疗方法。
Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation.