Passive or active immunization with myelin basic protein promotes recoveryfrom spinal cord contusion

Partial injury to the spinal cord can propagate itself, sometimes leading t o paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS ant igen 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 ac tive immunization with MBP promotes recovery from spinal cord injury. Anest hetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, us ing 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, Beatt ie, 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 < 0.0 03). In both cases, a single T cell treatment resulted in significantly bet ter recovery than that observed in control rats treated with T cells direct ed 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 r ecovery 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 ana lysis, immunohistochemical staining, and diffusion anisotropy magnetic reso nance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, ac hieved by either adoptive transfer or active immunization, enhances recover y from spinal cord injury by conferring effective neuroprotection. The auto immune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factor s whose production is locally regulated.