Michal Schwartz, Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.

We recently showed, against all expectations, that T cells directed against the CNS self antigen myelin basic protein (MBP), by reducing the post-traumatic spread of damage in the injured CNS, have a beneficial effect. We further proved, using morphological and functional criteria, that either passive or active immunization with myelin-associated antigens, or with cross-reactive synthetic antigens, promotes recovery of contused spinal cords or damaged optic nerves of adult rats. Our most recent results indicate that the observed neuroprotection is a physiological response, suggesting that trauma, at least in the central nervous system (CNS), evokes a stress signal that activates a purposeful benign T cell response directed against self antigens. It thus appears that (i) a stress signal transmitted from a traumatized tissue to the immune need not be pathogen-related, (ii) a response to self is not necessarily a mere fall-out from an aggressive response targeted on a pathogen, but may be a physiological event of benign intent, and (iii) an autoimmune response, provided that it is well regulated, need not pose a threat to the organism. We propose that immune cell therapy design should be based on timely intervention, with tight control of amounts and specificities so as to derive the maximal benefit with minimal risk.