 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, September 24, 2003, 23(25):8808-8819
Development/Plasticity/Repair
Vaccination with Dendritic Cells Pulsed with Peptides of Myelin Basic Protein Promotes Functional Recovery from Spinal Cord Injury
Ehud Hauben,1 * Amalia Gothilf,1 * Avi Cohen,2 * Oleg Butovsky,1 Uri Nevo,1,3 Igor Smirnov,2 Eti Yoles,2 Solange Akselrod,3 andMichal Schwartz1 1Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel, 2Proneuron Biotechnologies Limited, 74101 Ness-Ziona, Israel, and 3School of Physics and Astronomy, Tel-Aviv University, 69978 Tel-Aviv, Israel
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.
Key words: dendritic cells; autoimmunity; spinal cord injury (SCI); neuroprotection; neuroregeneration; inflammation; CNS trauma
Received May 8, 2003; revised June 30, 2003; accepted July 1, 2003.
This article has been cited by other articles:
S. Rossignol, M. Schwab, M. Schwartz, and M. G. Fehlings
Spinal Cord Injury: Time to Move?
J. Neurosci., October 31, 2007; 27(44): 11782 - 11792.
[Abstract] [Full Text] [PDF]
Y. Ziv, A. Finkelstein, Y. Geffen, J. Kipnis, I. Smirnov, S. Shpilman, I. Vertkin, M. Kimron, A. Lange, T. Hecht, et al.
A Novel Immune-Based Therapy for Stroke Induces Neuroprotection and Supports Neurogenesis
Stroke, February 1, 2007; 38(2): 774 - 782.
[Abstract] [Full Text] [PDF]
Y. Ziv, H. Avidan, S. Pluchino, G. Martino, and M. Schwartz
Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury
PNAS, August 29, 2006; 103(35): 13174 - 13179.
[Abstract] [Full Text] [PDF]
M. D. Boska, T. B. Lewis, C. J. Destache, E. J. Benner, J. A. Nelson, M. Uberti, R. L. Mosley, and H. E. Gendelman
Quantitative 1H Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy in an Animal Model of Parkinson's Disease
J. Neurosci., February 16, 2005; 25(7): 1691 - 1700.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|