CD8(+) phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis

We have recently described a novel population of CD8(+) phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent f rom axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8(+) phagocyte re sponse, we selectively depleted peripheral macrophages by systemic administ ration of dichloromethylene diphosphonate-filled liposomes prior to the ind uction of permanent ischemia by photothrombosis of cortical microvessels. M acrophage depletion led to a dramatic reduction but not complete abolishmen t of CD8(+) cells in the ensuing infarcts. Systemic administration of monoc lonal antibody Ox-8 eliminated CD8(+) cells from peripheral lymphoid organs but had no effect on CD8(+) phagocytes in the ischemic brain lesions. To f urther characterize the lesion conditions inducing the recruitment of CD8() phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannec rosis surrounded by areas with selective neuronal cell death. Recruitment o f CD8(+) phagocytes was restricted to areas of ischemic pannecrosis. In are as undergoing selective neuronal loss microglia up-regulated complement rec eptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), a nd to some extent expressed CD4, but not CD8 antigens. In conclusion our pr esent study shows that CD8(+) phagocytes in focal brain ischemia are predom inantly derived from hematogenous macrophages and selectively target to are as of ischemic pannecrosis.