Autophagy may cause the immune system to attack the central nervous system in models of multiple-sclerosis.
How autoreactive CD4+ T cells recognize their target antigen and induce sustained inflammation in organ-specific autoimmune diseases is incompletely understood. In an experimental model of multiple sclerosis, we show that accumulation of myelin-specific CD4+ T cells within the CNS and subsequent clinical disease development requires autophagy protein (ATG)-dependent phagocytosis in dendritic cells (DCs). Absence of ATG-dependent phagocytosis in DCs abrogates myelin presentation to CD4+ T cells following phagocytosis of oligodendroglial cells, and its pharmacological inhibition delays the onset and reduces the clinical severity of experimental autoimmune encephalomyelitis. Thus, DCs use ATG-dependent phagocytosis for enhanced presentation of myelin antigen during autoimmune CNS inflammation, thereby linking oligodendrocyte injury with antigen processing and autoimmune T cell pathogenicity.