Revisiting the Mechanisms of CNS Immune Privilege

Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.

TrendsThe meningeal space of the brain is enriched in various innate and adaptive immune cells that are communicating with and circulating through the deep cervical lymph nodes.Sufficient meningeal immunity is necessary for higher brain function: elimination of T cells results in cognitive deficiency in mice. T cells that are responsible for this beneficial crosstalk are presumably specific to CNS self-antigens.Close examination of the dura mater revealed the presence of functional classic lymphatic vessels that drain macromolecules and immune cells from the meninges and the CSF.Obstruction (surgical) or elimination (transgenic mice) of meningeal lymphatic vessels abrogates glymphatic flow and abolishes drainage to the deep cervical lymph nodes without affecting CSF pressure.