Immune regulatory and effector properties of human adult microglia studies in vitro and in situ.

Monocytes, macrophages, and brain microglia are the primary cell types most readily demonstrated to be infected in CNS lesions of patients infected with HIV (Koenig et al., 1986). Microglia are implicated in mediating CNS immune regulation and neural tissue injury associated with the AIDS-dementia syndrome. This report describes the isolation and characterization of microglia from the adult human central nervous system (CNS), and the assessment of microglial immune accessory/effector functions, some of which might be altered in CNS infectious and autoimmune diseases. In our studies we have compared the in vitro properties of microglia with peripheral blood monocytes/macrophages, and with astrocytes, a CNS cell type also implicated in contributing to immune regulatory and effector functions. Additionally, we have compared phenotypic features of resident microglia in situ with monocytes and macrophages that have infiltrated the CNS during the course of CNS inflammation. Our results suggest that adult human derived parenchymal microglia represent a unique cell of monocytic origin that can be distinguished both in vitro and in situ from monocytes/macrophages recently infiltrating into the CNS and from perivascular macrophages/microglial cells. Our data demonstrate that parenchymal microglia express several immune accessory/adhesion molecules that can provide second signals for CD4+T cell stimulation. Furthermore, microglia can synthesize cytokines and reactive oxygen species that may augment ongoing pathology in the CNS of AIDS patients. Infection of resident brain microglia could augment microglial immune accessory/effector functions possibly contributing to pathology seen in HIV dementia.