Boosting T-cell immunity as a therapeutic approach for neurodegenerative conditions: the role of innate immunity

Abstract

Our research group has been working for more than a decade on the cross-talk between the immune and the nervous systems. Due to the unique nature of the central nervous system (CNS) as an immune privileged site, it was commonly believed that the nervous system functions optimally without any immune intervention, and that any immune cell infiltration to the CNS is a sign of pathology. However, since the immune system constitutes the body's major defense and repair mechanism, it seemed unreasonable that the CNS would have completely lost the need for assistance from this system. This insight prompted us to revisit the entire question of whether immune cells are required for recovery from CNS injuries. We subsequently made numerous fundamental observations that led us to formulate a unified theory linking all neurodegenerative conditions; thus, we suggested that "T-cell immunity to self maintains the self," at least in the CNS. According to this view, immunity to self ("protective autoimmunity") provides a pivotal role in maintenance, protection, and repair of the healthy and diseased CNS. We further showed that the T cells mediate their effect, at least under pathological conditions, by controlling the recruitment of blood-borne monocytes, which play a crucial local role that cannot be replaced by the resident microglia. Boosting of such a T cell response specific for brain proteins, while carefully choosing the antigen, the carrier, timing, dosing, and regimen should be considered as a way of augmenting a physiological repair mechanism needed to ameliorate disease conditions while restoring equilibrium needed for protection, repair and renewal; such therapy is not intended to modify a single mediator of a single disease, but rather, would serve as an approach for adjusting the levels of the immune response needed to restore a lost balance.