HUMAN MICROGLIAL CELLS HAVE PHENOTYPIC AND FUNCTIONAL-CHARACTERISTICS IN COMMON WITH BOTH MACROPHAGES AND DENDRITIC ANTIGEN-PRESENTING CELLS

Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter, Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophages, Microglia have been implicated as the main antigen presenting cell within the CNS, and appear to be of central importance as effecters and regulators of demyelination. To further characterize the capacity for immune reactivity within the human CNS, we have studied several characteristics of microglia, both in situ and in vitro. We find that human microglia have ultrastructural, phenotypic (CD11c, CD68, acid phosphatase), and functional (FcR and CR mediated phagocytosis) properties typical for cells of the monocyte lineage. Our data indicate that microglia also have properties in common with dendritic antigen-presenting cells. Electron microscopy studies show extended dendritic cell processes on cultured microglia, and microglia are, like dendritic cells, negative for the monocyte markers nonspecific esterase, endogenous peroxidase, CD14, and RFD7. Microglia constitutively express HLA-DR in situ, and express the dendritic cell marker RFD1 upon activation, Coculturing of microglia with CD4(+) T cells results in clustering of T cells around microglia and initiation of a mixed lymphocyte reaction, both distinguishing features of dendritic cells. These functional properties of microglia may be of importance for the maintenance of an immunologic response in the CNS, an organ where dendritic cells, in contrast to other organs, have not previously been identified.