T cell-based therapeutic vaccination for spinal cord injury

Abstract

Spinal cord injury results in a massive loss of neurons, due not only to the direct effects of the primary injury but also to self-destructive processes triggered by the insult. Our group has recently reported that traumatic injury of the central nervous system (CNS) spontaneously evokes a purposeful T cell-mediated autoimmune response that reduces the injury-induced degeneration in the CNS; in its absence, the outcome of the injury is worse. Using a rat model of spinal cord contusion, we show here that this autoimmune protection can be induced and/or boosted by post-traumatic immunization with CNS myelin-associated self antigens such as myelin basic protein (MBP). In an attempt to reduce the risk of pathogenic autoimmunity while retaining the benefit of the immunization, we immunized spinally injured rats with MBP-derived peptides with attenuated pathogenic properties created by replacement of one amino acid in the T cell receptor-binding site. Immunization with these altered peptide ligands immediately after spinal cord contusion resulted in a significant improvement in recovery, assessed by locomotor activity in an open field. The feasibility of T cell-based vaccination, as opposed to vaccination mediated by antibodies for the treatment of nerve trauma, is further suggested by the relatively rapid onset of the T cell response following immunization. Such cell-mediated therapy is not only a way to evoke and boost a physiological remedy; it also has the advantage of being mediated by mobile cells, which can produce a variety of neurotrophic factors and cytokines in accordance with the tissue needs. T cells can also regulate other immune cells in a way that favors tissue maintenance and repair.