Protective autoimmunity as a T-cell response to central nervous system trauma: prospects for therapeutic vaccines.

Immune activity in general, and autoimmunity in particular, have long been considered as harmful in the context of central nervous system (CNS) trauma. Increasing evidence suggests, however, that the injured CNS can benefit from autoimmune manipulations. Active or passive immunization with CNS-associated self antigens was shown to promote recovery from a CNS insult. It is now also evident that this beneficial 'autoimmunity' is not solely an outcome of immune manipulation but is also a physiological response, evoked by a non-pathogenic insult and apparently designed to counteract the insult-related toxicity which is induced in part by essential physiological compounds present in excess of their normal levels. It appears that when the buffering capacity of constitutive local mechanisms (transporters, enzymes, etc.) that normally regulate these compounds is exceeded, assistance is recruited from the immune system. Like the overactive physiological compounds themselves, the immune system needs to be rigorously regulated in order to produce adequate phagocytic activity and the required quantity of cytokines and growth factors at the right time and place. Boosting of this autoimmune response is potentially a powerful strategy for neuroprotective therapy.