Vaccination with a Nogo-A-derived peptide after incomplete spinal-cord injury promotes recovery via a T-cell-mediated neuroprotective response: comparison with other myelin antigens.
The myelin-associated protein Nogo-A has received more research attention than any other inhibitor of axonal regeneration in the injured central nervous system (CNS). Circumvention of its inhibitory effect, by using antibodies specific to Nogo-A, has been shown to promote axonal regrowth. Studies in our laboratory have demonstrated that active or passive immunization of CNS-injured rats or mice with myelin-associated peptides induces a T-cell-mediated protective autoimmune response, which promotes recovery by reducing posttraumatic degeneration. Here, we show that neuronal degeneration after incomplete spinal-cord contusion in rats was substantially reduced, and hence recovery was significantly promoted, by posttraumatic immunization with p472, a peptide derived from Nogo-A. The observed effect seemed to be mediated by T cells and could be reproduced by passive transfer of a T cell line directed against the Nogo-A peptide. Thus, it seems that after incomplete spinal-cord injury, immunization with a variety of myelin-associated peptides, including those derived from Nogo-A, can be used to evoke a T cell-mediated response that promotes recovery. The choice of peptide(s) for clinical treatment of spinal-cord injuries should be based on safety considerations; in particular, the likelihood that the chosen peptide will not cause an autoimmune disease or interfere with essential functions of this peptide or other proteins. From a therapeutic point of view, the fact that the active cellular agents are T cells rather than antibodies is an advantage, as T cell production commences within the time window required for a protective effect after spinal-cord injury, whereas antibody production takes longer.
Hauben
E
E
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
Ibarra
A
A
Mizrahi
T
T
Barouch
R
R
Agranov
E
E
Schwartz
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000737:chemistry*; D009186:Myelin Sheath / Q000276:immunology*; D000070798:Nogo Proteins; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000941:Antigens; D009185:Myelin Proteins; D000070798:Nogo Proteins; D010446:Peptide Fragments; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D014612:Vaccines