Th cells recruit macrophages, which release proinflammatory cytokines and destructive molecules (such as nitric oxide [NO], IL1, IL6, tumor necrosis factor α [TNFα], and matrix metalloproteinases (MMPs]), and CD8 + T cells also directly attack MHC class I-expressing cells, such as oligodendrocytes and neurons [64, 65] . The secretion of destructive molecules, such as NO and TNFα, and the degradation of myelin are consequences of this cascade. TNF receptor 1 (TNFR1) but not TNFR2 signaling is critical for demyelination and the limitation of T-cell responses during immune-mediated CNS disease [66] . This complicated process triggers the recruitment of innate immune cells, generally consisting of T cells, macrophages, and microglia, which in turn mediate demyelination, axonal damage, and lesions.