Immune privilege of the brain

Based on Medawar's seminal experiments, the term ‘immunonologically privileged’, as reported by Billingham and Boswell in 1953, describes the brain's relative tolerance to grafts. While skin grafts were tolerated within the brain of rabbits, they were readily rejected upon placing a second graft of the same type under the skin of the same animal, thus demonstrating how immune tolerance can be overcome as reported by Medawar in 1948: “skin homografts transplanted to brain submit to, but cannot elicit an immune state”. Originally attributed to the absence of lymphatic vessels within the brain and (later) to the blood–brain barrier, immune privilege is now regarded also as a consequence of an immune-modulatory milieu brought about by various local cues, including matrix epitopes, neuropeptides, cytokines, death ligands and induction of indolamine 2,3-dioxygenase, which inhibit maturation of antigen-presenting cells to immunogenic dendritic cells and restrict proliferation and survival of lymphocytes. Since the only way to eliminate intracellular infectious agents relies on the elimination of all infected cells, and since this strategy may provide much more harm than help in the brain with its post-mitotic neurons, immune privilege and graft survival, respectively, can be regarded as the visible results of a multilayered safety mode favouring immune tolerance over elimination.