Mechanisms and implications of adaptive immune responses after traumatic spinal cord injury

Neuroscience, 2009 · DOI: 10.1016/j.neuroscience.2008.07.001 · Published: February 6, 2009

Simple Explanation

Traumatic spinal cord injury (SCI) can trigger the body's immune system to attack its own tissues, a process called autoimmunity. This involves immune cells like T and B lymphocytes, which normally defend against infections, but can become activated and target the nervous system after SCI. This autoimmune response can contribute to both the damage and repair processes following SCI. While it can worsen tissue injury, it can also promote the regeneration of nerve fibers. Researchers are exploring ways to manipulate this response to minimize the harmful effects while maximizing the beneficial ones. Understanding the specific antigens that the immune system targets after SCI is crucial. By identifying these targets, scientists hope to develop therapies that can selectively suppress the harmful autoimmune responses while preserving the helpful ones, ultimately leading to better outcomes for individuals with SCI.

Study Duration

Not specified

Participants

SCI humans and mice

Evidence Level

Review article

Key Findings

1
SCI activates MBP-reactive T cells capable of causing neuroinflammation and transient paralysis in rats, and the frequency of MBP-reactive T cells increases in SCI humans, reaching levels that approximate those seen in MS patients.
2
A significant percentage of SCI patients exhibit increased levels of serum and CSF antibodies specific for various CNS components like galactocerebroside, MBP, and GM-1 gangliosides, indicating a broad autoimmune response.
3
SCI induces a systemic autoimmune response, as evidenced by elevated CNS autoantibodies in the circulation of SCI mice, targeting a wide range of self-proteins beyond just those found in the nervous system.

Research Summary

Traumatic SCI triggers autoimmune reactions involving T and B cells, influencing post-traumatic inflammation, neurodegeneration, and repair processes. These lymphocytes are activated by SCI and play significant roles in shaping these cascades. The mechanisms of lymphocyte activation after SCI involve neuroantigens being released into the blood and lymphatics, leading to peripheral priming of autoimmunity. Activated T and B cells increase in secondary lymphoid organs and can cause paralysis and spinal cord inflammation in animal models. The implications of post-traumatic lymphocyte activation are complex, with evidence suggesting both exacerbation of tissue injury and promotion of CNS repair. Autoimmune responses can target various self-proteins, potentially contributing to systemic autoimmune disease and cognitive declines.

Practical Implications

Therapeutic vaccine development

Exploiting autoimmune-mediated repair by intentionally evoking autoimmune responses after SCI using active immunization or vaccine protocols to promote axon regeneration.

Antibody-based therapies

Utilizing passive delivery of autoantibodies as a repair strategy, such as injecting antibodies that bind to oligodendrocyte precursor cells to stimulate remyelination.

Targeted immunosuppression

Developing therapies to selectively suppress pathological effects of lymphocytes while boosting their reparative effects, without compromising host-defense mechanisms.

Study Limitations

1
The precise mechanisms responsible for triggering MS are still under controversy.
2
The functional implications of endogenous autoimmune responses triggered by SCI remain ill-defined and controversial.
3
The threshold for detecting changes caused by autoimmune processes may be extremely high after severe CNS injury.

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