Neuroprotective effect of vaccination with autoantigen-pulsed dendritic cells after spinal cord injury

J Surg Res. 2012 Jul;176(1):281-92. doi: 10.1016/j.jss.2011.06.066. Epub 2011 Jul 23.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Central Nervous System / immunology
  • Dendritic Cells / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Neuroprotective Agents / therapeutic use*
  • Recovery of Function / drug effects
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / prevention & control*
  • Treatment Outcome
  • Vaccines / pharmacology
  • Vaccines / therapeutic use*

Substances

  • Autoantigens
  • Neuroprotective Agents
  • Vaccines
  • Interleukin-12
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor