Therapeutic vaccination for spinal cord injury: helping the body to cure itself

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Abstract

Inflammation is thought to exacerbate the outcome of spinal cord injury. However, our findings have led us to view inflammation as a healing response that needs the help of a systemic immune response mediated by T helper 1 (Th1) cells that are specific to the abundant antigens residing in the lesion site. Strains differ in their ability to manifest, at the right time and intensity, a spontaneous T-cell response to antigens at the lesion site and therefore in their ability to generate a local inflammatory response whose outcome is beneficial (maintenance and repair). All strains, however, can benefit from immune intervention that boosts and regulates the inflammatory response. Because recovery comprises multi-step processes, pharmacological intervention will be less effective than well-synchronized, self-healing immune activity. Risk-free neuroprotective intervention might be achieved by post-traumatic vaccination with a weak, non-pathogenic, auto-antigen, causing autoimmune T cells to home to the lesion site where they become activated and therefore activate local phagocytic cells to remove hostile elements and provide growth factors.

Section snippets

Adaptive immunity, in the form of an immune response to self, as a defense mechanism

We have shown that passive transfer of autoimmune T cells into rats with either ONI or SCI results in improved recovery both morphologically and functionally 16, 18. Initially, this unexpected finding was received with skepticism because of the prevailing dogma that: (1) any immune activity in the CNS is detrimental; (2) autoimmunity is destructive; (3) passive transfer of autoimmune T cells is known to cause EAE; and (4) SCI in rats evokes an autoimmune response that in EAE-susceptible rats,

The outcome of well-controlled inflammation is beneficial

Our group has shown recently that after CNS insult, the naturally occurring CD4+CD25+ regulatory T (TRg) cells suppress the ability to manifest a protective T-cell-mediated response 35, 36. This cell population 37, 38 is the same as that discovered years ago and identified as thymus-derived suppressor T cells responsible for maintaining tolerance to self in the periphery [39]. Using transgenic mice that overexpress the T-cell receptor to myelin basic protein (tMBP/Rg+) [30], our group showed

Therapeutic boosting versus therapeutic suppression of inflammation after SCI

Recommendations from the National Acute Spinal Cord Injury Studies include the administration of high doses of intravenous MP as the standard method of treatment for patients with SCI [48]. However, the effect of MP treatment on the outcome of CNS injury is still a matter of controversy 49, 50, 51, 52.

If we assume that MP has some beneficial effect at an early stage after the insult, we need to consider how anti-inflammatory and pro-inflammatory treatments can be combined for the patient's

Concluding remarks

The findings outlined above indicate that induction of a well-controlled T-cell-based immune response against self-antigens residing in the lesion site that stimulates protective immunity without risk of triggering an autoimmune disease might be adopted as the basis for a potential therapeutic strategy for the treatment of SCI. Because both degeneration and repair of the damaged spinal cord are highly complex processes that comprise multiple operations, it is unlikely that a single intervention

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