Differential recruitment of CD8+ macrophages during Wallerian degenerationin the peripheral and central nervous system

The strong macrophage response occurring during Wallerian degeneration in t he peripheral but not central nervous system has been implicated in tissue remodeling and growth factor production as key requirements for successful axonal regeneration. We have previously identified a population of CD8+ pha gocytes in ischemic brain lesions that differed in its recruitment pattern from CD4+ macrophages/ microglia found in other lesion paradigms. In the pr esent study we show that crush injury to the sciatic nerve induced strong i nfiltration by CD8+ macrophages both at the crush site and into the degener ating distal nerve stump. At the crush site, CD8+ macrophages appeared with in 24 hours whereas infiltration of the distal nerve parenchyma was delayed to the second week. CD8+ macrophages were ED1+ and CD11b+ but always MHC c lass II-. Most CD8+ macrophages coexpressed CD4 while a significant number of CD4+/CD8-macrophages was also present. Expression of the resident tissue macrophage marker ED2 was largely restricted to the CD4+/CD8- population. Following intraorbital crush injury to the optic nerve, infiltration of CD8 + macrophages was strictly confined to the crush site. Taken together, our study demonstrates considerable spatiotemporal diversity of CD8+ macrophage responses to axotomy in the peripheral and central nervous system that may have implications for the different extent of axonal regeneration observed in both systems.