Enhanced Microglial Clearance of Myelin Debris in T Cell-Infiltrated Central Nervous System

Acute multiple sclerosis lesions are characterized by accumulation of T cells and macrophages, destruction of myelin and oligodendrocytes, and axonal damage. There is, however, limited information on neuroimmune interactions distal to sites of axonal damage in the T cell-infiltrated central nervous system. We investigated T-cell infiltration, myelin clearance, microglial activation, and phagocytic activity distal to sites of axonal transection through analysis of the perforant pathway deafferented dentate gyrus in SJL mice that had received T cells specific for myelin basic protein (T-MBP) or ovalbumin (T-OVA). The axonal lesion of T-MBP-recipient mice resulted in lesion-specific recruitment of large numbers of T cells in contrast of very limited T-cell infiltration in T-OVA-recipient and -naive perforant pathway-deafferented mice. By double immunofluorescence and confocal microscopy, infiltration with T-MBP but not T-OVA enhanced the microglial response to axonal transection and microglial phagocytosis of myelin debris associated with degenerating axons. Because myelin antigen-specific immune responses may provoke protective immunity, increased phagocytosis of myelin debris might enhance regeneration after a neural antigen-specific T cell-mediated immune response in multiple sclerosis.