Karimi Mohammad Hossein, Marzban Saeed, Hajiyan Mohammad Reza, Geramizadeh Bita, Pourfathollah Ali Akbar, Rajabiyan Mohammad Hassan, Ebrahimnezhad Salimeh
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Immunotherapy. 2015;7(2):111-8. doi: 10.2217/imt.14.112.
Tolerogenic dendritic cells (DCs) play a critical role in inducing and maintaining tolerance. CD40 is a member of tumor necrosis factor receptor super family and is a potent T-cell costimulatory molecule. Therefore, in this study we evaluated the effect of CD40 silenced DCs by RNA interference on mice skin allograft rejection.
MATERIALS & METHODS: Skin transplantation was performed from C57BL/6 to BALB/c mouse. Skin allograft recipients were assigned to four groups (n = 5). CD40 downregulated DCs were injected to the BALB/c mice intravenously 7 days before transplantation. Then, graft survival time, Treg generation, CD4(+) and CD8(+) T cells infiltration and cytokine levels in serum of this group were compared with those of untreated and cyclosporine groups.
In comparison with untreated group, BALB/c mice injected with CD40 siRNA transfected DCs showed an increased graft survival time, Treg cells, IL-4 and IL-10 cytokine levels as well as decreased number of intragraft CD4(+) and CD8(+) T cells. IFN-γ and IL-12 secretion were diminished, too.
Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.
耐受性树突状细胞（DCs）在诱导和维持免疫耐受中起关键作用。CD40是肿瘤坏死因子受体超家族的成员，是一种有效的T细胞共刺激分子。因此，在本研究中，我们评估了通过RNA干扰沉默CD40的DCs对小鼠皮肤同种异体移植排斥反应的影响。
将C57BL/6小鼠的皮肤移植到BALB/c小鼠身上。皮肤同种异体移植受体被分为四组（n = 5）。在移植前7天，将下调CD40的DCs静脉注射到BALB/c小鼠体内。然后，将该组的移植物存活时间、调节性T细胞（Treg）生成、CD4(+)和CD8(+) T细胞浸润以及血清中的细胞因子水平与未处理组和环孢素组进行比较。
与未处理组相比，注射了CD40 siRNA转染的DCs的BALB/c小鼠的移植物存活时间延长、Treg细胞增多、白细胞介素-4（IL-4）和白细胞介素-10（IL-10）细胞因子水平升高，同时移植物内CD4(+)和CD8(+) T细胞数量减少。干扰素-γ（IFN-γ）和白细胞介素-12（IL-12）的分泌也减少。
综上所述，这些数据表明DCs中CD40的下调可扩增Treg细胞并提高皮肤同种异体移植的存活率。
