Protective autoimmunity functions by intracranial immunosurveillance to support the mind: The missing link between health and disease.

Circulating immune cells support hippocampal neurogenesis, spatial memory, expression of brain-derived neurotrophic factor, and resilience to stress. Nevertheless, considering the immune privileged status of the central nervous system (CNS), such cells were assumed to be excluded from the healthy brain. It is evident, however, that the CNS is continuously surveyed by leukocytes, though their function is still a mystery. Coupling this routine leukocyte trafficking with the function attributed to circulating T cells in brain plasticity led us to propose here that CNS immunosurveillance is an integral part of the functioning brain. Anatomical restriction of selected self-recognizing leukocytes to the brain's borders and fluids (cerebrospinal fluid) not only supports the brain's activity, but also controls the potential aggressiveness of such cells. Accordingly, the brain's 'privilege' is its acquisition of a private peripheral immunological niche under its own control, which supports brain function. Immune malfunction may comprise a missing link between a healthy and diseased mind.