Neuroprotective Effect of Vaccination with Autoantigen-Pulsed Dendritic Cells After Spinal Cord Injury

Abstract

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.