Immune cell infiltration to the brain's territory was considered for decades to 
reflect a pathological process in which immune cells attack the central nervous 
system (CNS); such a process is observed in the inflammatory autoimmune disease, 
multiple sclerosis (MS). As neuroinflammatory processes within the CNS 
parenchyma are also common to other CNS pathologies, regardless of their 
etiology, including neurodegenerative disorders such as Alzheimer's disease (AD) 
and Amyotrophic lateral sclerosis (ALS), these pathologies have often been 
compared to MS, a disease that benefits from immunosuppressive therapy. Yet, 
over the last decade, it became clear that autoimmunity has a bright side, and 
that it plays a pivotal role in CNS repair following damage. Specifically, 
autoimmune T cells were found to facilitate CNS healing processes, such as in 
the case of sterile mechanical injuries to the brain or the spinal cord, mental 
stress, or biochemical insults. Even more intriguingly, autoimmune T cells were 
found to be involved in supporting fundamental processes of brain functional 
integrity, such as in the maintenance of life-long brain plasticity, including 
spatial learning and memory, and neurogenesis. Importantly, autoimmune T cells 
are part of a cellular network which, to operate efficiently and safely, 
requires tight regulation by other immune cell populations, such as regulatory T 
cells, which are indispensable for maintenance of immunological self-tolerance 
and homeostasis. Here, we suggest that dysregulation of the balance between 
peripheral immune suppression, on one hand, and protective autoimmunity, on the 
other, is an underlying mechanism in the emergence and progression of the 
neuroinflammatory response associated with chronic neurodegenerative diseases 
and brain aging. Mitigating chronic neuroinflammation under these conditions 
necessitates activation, rather than suppression, of the peripheral immune 
response directed against self. Accordingly, we propose that fighting off acute 
and chronic neurodegenerative conditions requires breaking peripheral immune 
tolerance to CNS self-antigens, in order to boost protective autoimmunity. 
Nevertheless, the optimal approach to fine tune such immune response must be 
individually explored for each condition.