Therapeutic Implications
The concept of protective autoimmunity is relatively new, and it has been shadowed by the historic and yet dominant view of autoimmunity as a damaging factor. Skepticism towards protective autoimmunity has been further fueled by the general concept of the CNS as being an immune privileged site in which immune cell activity is observed only under pathological conditions. Nevertheless, studies during the last decade have established that the immune system has the capacity to orchestrate a multitude of beneficial effects in the adult CNS under both normal and pathological conditions. Such effects range from the molecular level (growth factor production, buffering of toxic self compounds) through the cellular level (induction of axonal regrowth and neurogenesis) to the behavioral level (maintenance of spatial memory).
Several approaches have been used experimentally in order to harness naturally occurring immune cell activity in CNS pathologies. Here are key examples:
1. Therapeutic vaccination: This approach utilizes a common immunological manipulation. Inoculation of an antigen that is associated with the pathology, in this case the site of injury, evokes the activation and proliferation of lymphocytes which can specifically respond to the antigen used. For therapeutic purposes, vaccination with an antigen associated with the site of injury (for example peptides derived from myelin proteins) is problematic, because it carries the risk of inducing, in individuals susceptible to autoimmune diseases, an overwhelming inflammatory response that is detrimental for recovery. To circumvent this problem researchers have been using lower affinity agonists (termed ‘altered peptide ligands’) which induce a weaker immune response. Experiments in animal models of spinal cord injury revealed that the use of such altered peptide ligands is effective in promoting functional recovery without the risk of inducing a deleterious autoimmune response.
2. Alteration of regulatory T cell activity: Suppressing regulatory T cell activity following injury can allow a more robust autoimmune response to take place. For therapeutic purpose, the mere removal of regulatory T cells is, again, highly problematic because it increases the risk of inducing autoimmune diseases. Overcoming this limitation is possible using agents that transiently suppress regulatory T cell activity. Such an agent has been used successfully in an animal model of ischemic stroke, where treated animals exhibited improved neurological recovery relative to non-treated animals.
Read more about this topic: Protective Autoimmunity
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