Bone marrow derived elements and resident microglia in brain inflammation.
Infection of the central nervous (CNS) system by the human immunodeficiency virus (HIV) depends on the migration of infected hematogenous cells into the brain. We thus used quantitative light and electron microscopic immunocytochemistry to study the homing and turnover of bone marrow derived cells in the CNS in radiation bone marrow chimeras under normal conditions and in experimental autoimmune encephalomyelitis (EAE) as an experimental model of brain inflammation. Our studies suggest the following conclusions. First, the central nervous system is continuously patrolled by a small number of T-lymphocytes and monocytes. Meningeal and perivascular monocytes are slowly replaced by hematogenous cells under normal conditions, and this turnover is accelerated in the course of inflammation. In contrast, resident microglia represent a very stable cell pool, which in adult animals is only exceptionally replaced by hematogenous cells, even after recovery from severe brain inflammation. Second, although in bone-marrow-chimeric animals resident microglia, astrocytes, and ependymal cells are not able to present antigen to Lewis T-lymphocytes, the inflammatory reaction in EAE is qualitatively and quantitatively similar in these animals compared to fully histocompatible Lewis rats. Finally, resident microglia express the macrophage activation antigen ED1. Thus, microglia cells appear to function as effector cells in EAE lesions.
Lassmann
H
H
Research Unit for Experimental Neuropathology, Austrian Academy of Sciences, Vienna.
Schmied
M
M
Vass
K
K
Hickey
W F
WF
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology* / Q000528:radiation effects; D002678:Chimera; D004660:Encephalitis / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D007150:Immunohistochemistry; D008578:Meninges / Q000473:pathology; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000276:immunology; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew
D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein