Department of Orthopedics, First Affiliated Hospital, Harbin Medical University, Harbin, PR China.
J Surg Res. 2012 Jul;176(1):281-92. doi: 10.1016/j.jss.2011.06.066. Epub 2011 Jul 23.
Studies have shown that the development of a properly controlled autoreactive T cell response can serve as a therapeutic approach for spinal cord injury (SCI). Thus, vaccination with mature dendritic cells (DCs) pulsed with central nervous system (CNS) antigens that can prime autoreactive T cells have the potential for treating SCI.
Mature DCs pulsed with spinal cord homogenate (SCH), nonpulsed mature DC or phosphate-buffer solution (PBS) were injected into spinal cord-injured mice peritoneally. The functional recovery of spinal cord was measured by Basso mouse scale and footprint analysis. Spinal cord specimen was preserved for immunohistochemical staining to detect T cell infiltration, differentiation of neural stem/progenitor cells, and tissue preservation. RT-PCR and enzyme linked immunosorbent assay (ELISA) was used to detect the expression of cytokines and neurotrophic factors.
Vaccination with DCs pulsed with SCH promoted pronounced functional recovery from SCI. The neuroprotection induced by SCH-pulsed DCs (SCH-DC) correlated to the accumulation of CD4(+) T cells in the lesion site. SCH-DC markedly affected the production of interferon-γ, interleukin-12, and granulocyte-macrophage colony stimulating factor. SCH-DC also promoted expression of neurotrophic factors in the injured spinal cord and spleen cells. Furthermore, vaccination with SCH-DC enhanced neuronal differentiation of neural stem/progenitor cells, and it led to better tissue preservation.
The results of the present study suggest that DC-mediated immune regulation may be a potential therapeutic approach aimed at shifting the balance between immune and nerve cells in order to treat SCI.
研究表明，适当控制自身反应性 T 细胞反应的发展可以作为治疗脊髓损伤（SCI）的一种方法。因此，用中枢神经系统（CNS）抗原冲击成熟树突状细胞（DC）进行疫苗接种，能够刺激自身反应性 T 细胞，具有治疗 SCI 的潜力。
将脊髓匀浆（SCH）冲击成熟的 DC、未冲击的成熟 DC 或磷酸盐缓冲液（PBS）注入脊髓损伤的小鼠腹腔内。通过 Basso 小鼠量表和足迹分析来测量脊髓的功能恢复。保存脊髓标本进行免疫组织化学染色，以检测 T 细胞浸润、神经干细胞/祖细胞的分化和组织保存情况。使用 RT-PCR 和酶联免疫吸附试验（ELISA）检测细胞因子和神经营养因子的表达。
用 SCH 冲击成熟的 DC 进行疫苗接种可显著促进 SCI 的功能恢复。SCH 冲击成熟的 DC（SCH-DC）诱导的神经保护作用与病变部位 CD4+T 细胞的积累相关。SCH-DC 明显影响干扰素-γ、白细胞介素-12 和粒细胞-巨噬细胞集落刺激因子的产生。SCH-DC 还促进了损伤脊髓和脾细胞中神经营养因子的表达。此外，SCH-DC 增强了神经干细胞/祖细胞的神经元分化，并导致更好的组织保存。
本研究结果表明，DC 介导的免疫调节可能是一种有潜力的治疗方法，旨在改变免疫和神经细胞之间的平衡，以治疗 SCI。
