Zhao Jun, Li Zhaohui, Wang Lei, Liu Jing, Wang Dajiang, Chen Guoling, Wang Qi, Zhang Han
Department of Ophthalmology, The 2nd Hospital of Shandong University, Jinan 250031, China; Department of Ophthalmology, General Hospital of Liaohe Oil Field, Panjin 124000, China.
The General Hospital of PLA, Beijing 100853, China.
Transpl Immunol. 2015 Nov;33(3):192-7. doi: 10.1016/j.trim.2015.09.003. Epub 2015 Sep 28.
The study aimed to investigate whether Foxp3-expressing sensitized Teff cells could inhibit allograft rejection in corneal allograft transplantation mouse model.
Foxp3-expressing sensitized Teff cells were constructed by transfection of retroviral expression plasmid expressing Foxp3 into the sensi-Teff cells from a Balb/c mouse immunized by C57BL/6(H2b) mouse splenocytes. Balb/c mice were randomly divided into 5 groups: Four groups received tail vein injection of Foxp3-expressing sensitized Teff cells, or Foxp3-expressing Teff cells, or Treg cells or no intervention 1 day prior to corneal allograft transplantation. C57BL/6(H2b) was the donor mouse. The last group received corneal autograft transplantation. Corneal allograft survival time and percentage of CD4(+) T cells were detected. ELISPOT and Footpad swelling test were used to measure IL-2 and IFN-γ, and delayed-type hypersensitivity (DTH) response, respectively.
Mice that had received an injection of Foxp3-expressing sensitized T cells prior to an allograft corneal transplantation, showed significantly longer survival time of corneal allograft, decreased percentage of CD4(+) T cells, IL-2 and IFN-γ, and alleviated footpad swelling than the mice that had received either Foxp3-Teff or Treg cells.
Foxp3-sensi-Teff cell treatment that prolongs corneal allograft survival in the mouse model, might partly through suppressing CD4(+) T cells, IL-2 and IFN-γ.
本研究旨在探讨表达Foxp3的致敏效应T细胞是否能抑制角膜移植小鼠模型中的同种异体移植排斥反应。
通过将表达Foxp3的逆转录病毒表达质粒转染至经C57BL/6（H2b）小鼠脾细胞免疫的Balb/c小鼠的致敏效应T细胞中，构建表达Foxp3的致敏效应T细胞。将Balb/c小鼠随机分为5组：四组在角膜同种异体移植前1天接受尾静脉注射表达Foxp3的致敏效应T细胞、或表达Foxp3的效应T细胞、或调节性T细胞，或不进行干预。C57BL/6（H2b）为供体小鼠。最后一组接受角膜自体移植。检测角膜同种异体移植存活时间和CD4(+) T细胞百分比。分别采用酶联免疫斑点法（ELISPOT）和足垫肿胀试验检测白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）以及迟发型超敏反应（DTH）。
在同种异体角膜移植前接受表达Foxp3的致敏T细胞注射的小鼠，其角膜同种异体移植的存活时间显著延长，CD4(+) T细胞、IL-2和IFN-γ的百分比降低，足垫肿胀减轻，优于接受Foxp3-效应T细胞或调节性T细胞的小鼠。
在小鼠模型中，Foxp3致敏效应T细胞治疗可延长角膜同种异体移植的存活时间，可能部分是通过抑制CD4(+) T细胞、IL-2和IFN-γ实现的。
