T Cell Entry into the CNS: How Myelin is Presented Burkhard Becher Institute of Experimental Immunology, University of Zurich, Switzerland
The CNS is under close surveillance by immune cells, which mediate tissue homeostasis, protection and repair. Conversely, in neuroinflammation, dysregulated leukocyte invasion into the CNS, leads to immunopathology and neurological disability. To invade the brain parenchyma, autoimmune encephalitogenic T helper (Th) cells must encounter their cognate antigens (Ags) presented via local Ag-presenting cells (APCs). The precise identity of the APC, which samples, processes and presents neuro-Ag to auto-aggressive T cells is unknown. Dendritic cells (DCs), border-associated macrophages (BAMs) and microglia have been implicated as the pertinent APC. Here, we used a combination of high-dimensional single-cell mapping and conditional MHC-class II ablation across all CNS APCs to systematically interrogate each population for its ability to reactivate encephalitogenic Th cells in vivo. We found a rare population of conventional dendritic cells (cDCs) to be essential for licensing T cells to initiate neuroinflammation, whereas neither microglia nor BAMs were able to do so.