Vaccination with dendritic cells pulsed with peptides of myelin basic protein promotes functional recovery from spinal cord injury

Ehud Hauben, Amalia Gothilf, Avi Cohen, Oleg Butovsky, Uri Nevo, Igor Smirnov, Eti Yoles, Solange Akselrod, Michal Schwartz

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Injury-induced self-destructive processes cause significant functional loss after incomplete spinal cord injury (SCI). Cellular elements of both the innate (macrophage) and the adaptive (T-cell) immune response can, if properly activated and controlled, promote post-traumatic regrowth and protection after SCI. Dendritic cells (DCs) trigger activation of effector and regulatory T-cells, providing a link between the functions of the innate and the adaptive immune systems. They also initiate and control the body's response to pathogenic agents and regulate immune responses to both foreign and self-antigens. Here we show that post-injury injection of bone marrow-derived DCs pulsed with encephalitogenic or nonencephalitogenic peptides derived from myelin basic protein, when administered (either systemically or locally by injection into the lesion site) up to 12 d after the injury, led to significant and pronounced recovery from severe incomplete SCI. No significant protection was seen in DC recipients deprived of mature T-cells. Flow cytometry, RT-PCR, and proliferation assays indicated that the DCs prepared and used here were mature and immunogenic. Taken together, the results suggest that the DC-mediated neuroprotection was achieved via the induction of a systemic T-cell-dependent immune response. Better preservation of neural tissue and diminished formation of cysts and scar tissue accompanied the improved functional recovery in DC-treated rats. The use of antigen-specific DCs may represent an effective way to obtain, via transient induction of an autoimmune response, the maximal benefit of immune-mediated repair and maintenance as well as protection against self-destructive compounds.

Original languageEnglish
Pages (from-to)8808-8819
Number of pages12
JournalJournal of Neuroscience
Volume23
Issue number25
DOIs
StatePublished - Sep 24 2003
Externally publishedYes

Keywords

  • Autoimmunity
  • CNS trauma
  • Dendritic cells
  • Inflammation
  • Neuroprotection
  • Neuroregeneration
  • Spinal cord injury (SCI)

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