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The Journal of Neuroscience, September 1, 2000, 20(17):6421-6430
Passive or Active Immunization with Myelin Basic Protein Promotes Recovery from Spinal Cord Contusion
Ehud Hauben1, Oleg Butovsky1, Uri Nevo1, 4, Eti Yoles1, Gila Moalem1, 2, Eugenia Agranov5, Felix Mor2, Raya Leibowitz-Amit1, Evgenie Pevsner6, Solange Akselrod4, Michal Neeman3, Irun R. Cohen2, and Michal Schwartz1 Departments of 1 Neurobiology, 2 Immunology, and 3 Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel, 4 Department of Medical Physics, Tel-Aviv University, Tel-Aviv 69978, Israel, 5 Beit Levinstein Hospital, Raanana 43100, Israel, and 6 Department of Neurosurgery, Sheba Medical Center, Tel-Aviv University, Tel-Aviv 52621, Israel
Partial injury to the spinal cord can propagate itself, sometimes leading to paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS antigen myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in rats. Here we show that not only transfer of T cells but also active immunization with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, using the New York University impactor, were injected systemically with anti-MBP T cells at the time of contusion or 1 week later. Another group of rats was immunized, 1 week before contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional recovery was assessed in a randomized, double-blinded manner, using the open-field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of contusion at T7 differed from that at T9 (2.9 ± 0.4, n = 25, compared with 8.3 ± 0.4, n = 12; p < 0.003). In both cases, a single T cell treatment resulted in significantly better recovery than that observed in control rats treated with T cells directed against the nonself antigen ovalbumin. Delayed treatment with T cells (1 week after contusion) resulted in significantly better recovery (7.0 ± 1; n = 6) than that observed in control rats treated with PBS (2.0 ± 0.8; n = 6; p < 0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score of 6.1 ± 0.8 (n = 6) compared with a score of 3.0 ± 0.8 (n = 5; p < 0.05) in control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical staining, and diffusion anisotropy magnetic resonance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, achieved by either adoptive transfer or active immunization, enhances recovery from spinal cord injury by conferring effective neuroprotection. The autoimmune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factors whose production is locally regulated.
Key words: CNS; beneficial autoimmunity; myelin basic protein; neurofilaments; spinal cord injury; secondary degeneration; neuroprotection; EAE
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176421-10$05.00/0
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