Multifaceted interactions between adaptive immunity and the central nervous system

Abstract

Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence. This Review summarizes the current standing of and challenging questions related to interactions between adaptive immunity and the CNS and considers the possible directions in which these aspects of neuroimmunology will be heading over the next decade.

Brain perivascular macrophages: characterization and functional roles in health and disease

“…However, since CLO depletes both MGM and PVM, the observed effects cannot be attributed exclusively to PVM. Considering the emerging role of meningeal immune cells in brain function [72], more detailed studies are needed to elucidate the relative contribution of PVM and MGM in health and disease. Furthermore, the changes that brain diseases induce in PVM and the molecular determinants driving their beneficial or deleterious effects on disease outcome remain unclear.…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…Many other ions and proteins are transported through the choroid plexus epithelium and diffuse from the CSF into the brain, where they affect neuronal function (94). More recently, the immune compartment in the meninges was implicated in neuronal function (75). Notably, IL-4 and IL-13 production by meningeal T cells appears to contribute to the maintenance of cognitive function in mice (74,95).…”

“…The brain's parenchymal and CSF/meningeal compartments possess different properties that confer on each a unique immune status. Under physiological conditions, numerous immune cells carry out CNS surveillance and occupy the CSF/meningeal compartment (45,(74)(75)(76). Meningeal ECs lack astrocytic end-feet and also differ in other ways from brain ECs.…”

How and why do T cells and their derived cytokines affect the injured and healthy brain?

“…In the absence of infection, an immune response directed towards the CNS has typically been considered pathogenic. However, it is only recently that we have started to appreciate that immune surveillance of the CNS is crucial for correct brain function and recovery after injury 2 .…”

“…1). According to currently proposed models, T cells enter the meninges and the CSF through blood vessels in the leptomeninges (the pia mater and arachnoid), through meningeal blood vessels in the dura, or through the choroid plexus 111,112 , and exit to the deep cervical lymph nodes through meningeal lymphatic vessels 2,113,114 . Using intravital two-photon microscopy, Schläger et al .…”