The CNS Immune Landscape from the Viewpoint of a T Cell

Neuro-immune interactions are not only vital for the control of neurotropic pathogens, but also appear to influence brain development and homeostasis. During immune surveillance, T cells can patrol the CNS-associated border regions to sense pathogenic alterations. While access to the CNS parenchyma is restricted in the steady state, various disease processes can initiate parenchymal T cell CNS invasion. However, to breach the glia limitans, T cells must become reactivated within the meningeal spaces. T cells cannot sense native antigens (Ags), but instead recognize small processed peptides bound to MHC molecules and presented on the surface of Ag-presenting cells (APCs). In this review, we focus on (CD4⁺) T cell-CNS interactions that are dependent on Ag recognition. We discuss the potential paths and mechanisms of T cell entry into the CNS, in particular with respect to CNS-resident APCs, which present CNS-derived Ag in the absence of inflammation.